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.

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.

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.

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.

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.

Day case surgery training for surgical trainees: a disappearing act?

INTRODUCTION: Over the past decade there has been considerable change to surgical training such as modernising medical careers which have raised concerns over exposure to operative experience. With the National Health Service (NHS) plan aiming for the majority of elective surgical cases to be performed as day cases we sought to assess the level of exposure modern day surgical trainees obtain in day case surgery. METHODS: An anonymous electronic questionnaire survey was completed by 100 surgical trainees in surgical training across the United Kingdom (UK) from a variety of sub-specialities. 16 questions pertinent to day case surgery exposure were answered. RESULTS: The majority of the trainees who completed the survey felt day case surgery is a vital part of their training as a surgeon. Only less than one-third of all the trainees had formal timetabled day case surgery lists. Of the 31 trainees who had scheduled day lists only 58% (n = 18) were consistently able to attend. The most common reasons for being unable to attend were rota issues and lack of encouragement from seniors. 90 trainees (90%) were not satisfied with their overall Day Case Surgery training. CONCLUSIONS: The survey reveals that the modern surgical trainee is gaining a low and inconsistent level of exposure to day case surgery despite being aware of the importance of this modality of training. An urgent review is required to ensure trainees become actively involved in day case surgery and are not missing on this vital training opportunity.

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.

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.

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.

A blinded, randomised, controlled trial of stapled versus tissue glue closure of neck surgery incisions.

INTRODUCTION: Cosmetic acceptability of scar and neck mobility are important outcomes after collar line incision for neck surgery. This randomised, controlled trial compares these parameters in closures using tissue glue (Dermabond, Ethicon, UK) and skin staples. PATIENTS AND METHODS: Patients requiring a collar line incision were randomised to receiving tissue glue or staples for skin closure. Time for closure to be completed was recorded. Mobility of the neck was assessed using a visual analogue scale at 48 h and 1 week after surgery. At 6 weeks, cosmetic appearance was assessed using a linear 1-10 visual analogue scale by the patient, surgeon and an independent blinded assessor. Results were compared using appropriate statistical tests. RESULTS: Glued (n = 14) and stapled (n = 15) closures were performed for hemithyroidectomy (n = 8 versus 6), sub-total thyroidectomy (n = 2 versus 4), total thyroidectomy (n = 1 versus 4) and parathyroidectomy (n = 3 versus 1). Closure with tissue glue took significantly longer than with staples (mean, 95 versus 28 s; P < 0.001). Neck mobility scores were comparable at 48 h and 1 week (mean, 4.8 versus 4.4; P = 0.552: and 2.7 versus 2.6; P = 0.886). Cosmetic appearance at 6 weeks was comparable when patient (mean, 1.7 versus 1.8; P = 0.898), surgeon (mean, 2.6 versus 2.3; P = 0.633) and independent assessment (mean, 1.4 versus 1.9; P = 0.365) was performed. CONCLUSIONS: The use of glued skin closure may increase the duration of surgery but acceptable neck mobility and wound cosmesis can be achieved by the more rapid application of stapled skin closure in cervicotomy incisions.

Sperm competition and male ejaculate investment in Nauphoeta cinerea: effects of social environment during development.

Selective pressure arising from sperm competition has been predicted to influence evolutionary and behavioural adjustment of ejaculate investment, but also may influence developmental adjustment of ejaculate investment. Immature males able to target resources strategically based on the competitive environment they will experience when they become sexually mature should be at a selective advantage. In our study we investigated how the presence of potential competitors or mates affects ejaculate and testes investment during development in the cockroach Nauphoeta cinerea, a species where males control female remating via their ejaculate size (large spermatophores prevent females from remating and therefore function to avoid sperm competition for males) and females store sperm. Our aim was to determine whether the social environment influences developmental adjustment of ejaculate investment and the relative importance of ejaculate components with different functions; avoidance of or engagement in sperm competition. We conclude that the social environment can influence developmental and behavioural flexibility in specific ejaculate components that may function to avoid or engage in sperm competition.

Endoscopic laser ablation of advanced rectal carcinoma--a DGH experience.

BACKGROUND: Patients with inoperable advanced rectal carcinoma require palliation for local symptoms. Endoscopic Nd-Yag laser ablation is a valid palliative treatment option in patients with advanced rectal carcinoma who are poor operative risks due to coexistent multiple comorbidities. METHODS: All patients who cannot undergo radical surgery due to various factors such as tumour size, poor risk patients, distant metastasis and refusal to undergo surgery were offered palliation with endoscopic Nd-YAG laser ablation. Indications included troublesome bleeding, local recurrence, mucous discharge and impending obstruction. Patients were admitted on the day of treatment, phosphate enema given for bowel preparation and endoscopic ablation done through a flexible sigmoidoscope under intravenous sedation with midazolam. All patients were discharged the next day after overnight observation. Patients were reviewed every 3 months and laser ablation repeated if deemed necessary. RESULTS: Eleven patients (7 males, 4 females; mean age 83.6 years, range 77-90 years) underwent endoscopic laser ablation in a District General Hospital --8 for rectal carcinoma, 2 for rectosigmoid tumour and 1 for recurrent tubulovillous adenoma. The number of treatment episodes varied from 1 to 12 with symptom free interval from 2 to 18 months between treatment episodes. There were 3 failures, one patient required defunctioning colostomy, one patient was referred for radiotherapy due to persistent symptoms and in one patient laser treatment had to be abandoned due to local extent. There were no immediate post-treatment complications, but one patient developed incontinence after 5 episodes which might be attributable to tumour infiltration. DISCUSSION: Endoscopic laser ablation is a practical and feasible alternative to other palliative treatment modalities in the management of this unfortunate category of patients due to low morbidity and mortality, short hospitalization and low complication rates.

Comparison of rigid vs flexible sigmoidoscopy in detection of significant anorectal lesions.

OBJECTIVE: Sigmoidoscopy is an essential tool in colorectal clinics in the detection of anorectal lesions including rectosigmoid adenomas and carcinomas. However, rigid sigmoidoscope (RS) is still more widely used than flexible sigmoidoscope (FS) as the primary investigation, despite the fact that the latter is more comfortable to the patient and has greater diagnostic yield. Hence we wanted to compare the two modalities in terms of diagnostic use for picking up significant anorectal lesions. METHODS: A retrospective review of all patients referred to the colorectal clinic who had undergone both rigid and flexible sigmoidoscopy for investigation of colorectal symptoms in 2001 was done. Findings recorded during rigid and flexible sigmoidoscopy including depth of insertion, site of lesion and complications were analysed. RESULTS: 152 patients underwent both rigid and flexible sigmoidoscopy as part of investigation of colorectal symptoms. Of the 115 (75.6%) declared normal by RS, 39 (33.9%) had significant lesions including 7 polyps and 4 malignant lesions within 20 cm of the anal verge during FS. Of the 31 patients (20.4%) in whom RS was not helpful due to faecal loading, 15 (48.4%) had significant lesions including 4 malignancies and 1 polyp --all within 20 cm of the anal verge during FS. Only 2 polyps and 1 malignant lesion were picked up by both flexible and rigid sigmoidoscopy. There were no complications in both procedures. CONCLUSION: Since flexible sigmoidoscopy is superior to rigid sigmoidoscopy in terms of patient comfort, diagnostic value and ease of doing procedures like biopsy and polypectomy; it can be used as a front line investigation to exclude colorectal pathology in out patient clinics. The utility of rigid sigmoidoscope is in question and in view of obvious shortcomings, may be replaced by flexible sigmoidoscopy, though obvious resource constraints need to be considered.

Sexual conflict and cooperation under naturally occurring male enforced monogamy.

An evolutionary conflict often exists between the sexes in regard to female mating patterns. Females can benefit from polyandry, whereas males mating with polyandrous females lose reproductive opportunities because of sperm competition. Where this conflict occurs, the evolution of mechanisms whereby males can control female remating, often at a fitness cost to the female, are expected to evolve. The fitness cost to the female will be increased in systems where a few high status males monopolise mating opportunities and thus have limited sperm supplies. Here we show that in the cockroach Nauphoeta cinerea, a species where males enforce female monogamy in the first reproductive cycle, males that have become sperm depleted continue to be able to manipulate female remating behaviour. Although the manipulation severely decreases fecundity in females mated to sperm-depleted males, males benefit, increasing their relative fitness by preventing other males from reproducing. Our results suggest that there is selection on maintaining the mechanism of manipulation rather than maintaining sperm numbers. Taken with previous research on sexual conflict in N. cinerea, this study suggests that the causes and consequences of sexual conflict are complex and can change across the life history of an individual.