Signalling of information that is neither cryptic nor private.

It is commonly assumed that in order for animal signals to be advantageous, the information being signalled could not have been obtained otherwise, and is therefore 'cryptic' or 'private'. Here, we suggest a scenario in which individuals can gain an advantage by signalling 'public' information that is neither cryptic nor private. In that scenario, signalling increases the efficiency with which that 'public' information is transmitted. We formalize our idea with a game in which offspring can signal their condition to their parents. Specifically, we consider a resource-strapped parent who can only invest in one of its two offspring, and we allow offspring the chance to influence parental investment through a signal. A parent in the game seeks to invest in the higher-quality offspring, which it could identify either through a publicly available cue, such as body size, or by relying on a signal provided by the offspring. We find that if the signal can convey information about offspring quality more efficiently than cues, then signalling of condition between offspring and parents can be favoured by selection, even though parents could potentially have acquired the same information from the cue. Our results suggest that the biological function of signals may be broader than currently considered, and provide a scenario where low cost signalling can be favoured. More generally, efficiency benefits could explain signalling across a range of biological and economic scenarios.

The association between the emergence of cooperative breeding and clutch size.

Previous theoretical work has suggested that smaller brood sizes helped facilitate the emergence of cooperative breeding in birds. However, recent empirical evidence has found no statistically significant difference between the clutch sizes of cooperative breeders and that of noncooperative breeders. One explanation for this finding is that while small clutch sizes may predispose species to cooperative breeding, the emergence of cooperative breeding itself may influence the evolution of clutch size. Here, we develop a set of models using population dynamics to describe how the emergence of cooperative breeding influences clutch size. We find, in contrast to previous theoretical work, that the emergence of cooperative breeding does not necessarily decrease (and under certain conditions may actually increase) clutch size. In particular, clutch size may increase after the emergence of cooperative breeding if helpers--philopatric individuals that assist their breeding relatives--are able to substantially improve breeder fecundity at low costs to their own survival, and if the association between breeder and helper is brief. In many cases, clutch size increases following the emergence of cooperative breeding not because it is optimal for the breeder, but as the result of breeder-helper conflict over resource allocation.

Quality not quantity for transglutaminase antibody 2: the performance of an endomysial and tissue transglutaminase test in screening coeliac disease remains stable over time.

National Institute of Clinical Excellence (NICE) and European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) guidance for the diagnosis of coeliac disease has been published. However, there is some controversy regarding the advice on the use of stratifying levels of immunoglobulin (IgA) tissue transglutaminase antibody (TG2) test positivity in the absence of test standardization and the vagueness of the indication to test equivocal samples. Using repeat service audit, we demonstrate that a combination of TG2 followed by IgA endomysial antibodies (EMA) is the best strategy for all degrees of mucosal abnormality using our test combination. Reliance upon immunoassay titre is not as effective, and cannot be applied consistently across populations in the absence of assay standardization. Guidelines advocating the use of tests should involve experts in laboratory diagnostics and external quality assurance to ensure that errors of generalization do not occur and that test performance is achievable in routine diagnostic use.

Serological testing for coeliac disease in Type 1 diabetes mellitus: is immunoglobulin A level measurement necessary?

AIMS: Immunoglobulin A (IgA) measurement is advocated when case finding for coeliac disease in patients with Type 1 diabetes mellitus. Currently, there is a paucity of contemporary studies assessing IgA deficiency in Type 1 diabetes. This study evaluates the prevalence of IgA deficiency in individuals with Type 1 diabetes, compared with patients with coeliac disease and control subjects. In addition, we evaluate whether routine IgA measurement is justifiable when case finding for coeliac disease in patients with Type 1 diabetes. METHODS: All patients were assessed using IgA endomysial antibodies, IgA anti-tissue transglutaminase antibodies and total IgA levels. Altogether, 2434 individuals were tested: 1000 patients with Type 1 diabetes, 234 patients with coeliac disease and 1200 population control subjects. Definitive IgA deficiency was defined as total IgA levels < 0.07 g/l. RESULTS: The prevalence of IgA deficiency was significantly more common in patients with Type 1 diabetes (0.9%, n = 9/1000; P = 0.036) and coeliac disease (1.29%, n = 3/234; P = 0.041) when compared with population control subjects (prevalence of 0.17%, 2/1200). No statistical difference between Type 1 diabetes and coeliac disease for IgA deficiency was identified (P = 0.87). Of patients in the group with Type 1 diabetes, 3.3% (33/1000) had coeliac disease, and of those only one patient had IgA deficiency leading to an antibody-negative presentation. Both IgA-deficient individuals within the population control subjects had normal duodenal biopsies and no relevant symptoms. CONCLUSIONS: IgA deficiency is more common in Type 1 diabetes compared with population control subjects. Despite this, very few individuals with Type 1 diabetes and IgA deficiency appear to have villous atrophy on biopsy. These outcomes question the practice of routine IgA measurement when case finding for coeliac disease in patients with Type 1 diabetes.

Raised tryptase without anaphylaxis or mastocytosis: heterophilic antibody interference in the serum tryptase assay.

Mast cell tryptase (MCT) is a key diagnostic test for mastocytosis and anaphylaxis. High serum tryptase levels are also one of the risk factors for adverse reaction in venom immunotherapy, yet occasional patients are seen with raised levels in the absence of either diagnosis. False positive results can be due to assay interference by heterophilic antibodies such as rheumatoid factor (RF) and human anti-mouse antibodies (HAMA). We therefore investigated heterophilic antibody interference by rheumatoid factor activity and HAMA as a cause of raised MCT results in the Phadia tryptase assay. Serum samples from 83 patients were assayed for MCT and rheumatoid factor before and after the use of heterophilic antibody blocking tubes (HBT). Samples with more than 17% reduction in MCT with detectable RF were then assayed for HAMA. Fourteen (17%) of the 83 samples with positive RF showed a >17% decrease in mast cell tryptase after HBT blocking. Post-HBT, eight of 14 (57%) reverted from elevated to normal range values with falls of up to 98%. RF levels were also decreased significantly (up to 75%). Only one of the 83 tested was apparently affected by HAMA in the absence of detectable IgM RF. In conclusion, any suspicious MCT result should be checked for heterophilic antibodies to evaluate possible interference. False positive MCT levels can be caused by rheumatoid factor. We suggest a strategy for identifying assay interference, and show that it is essential to incorporate this caveat into guidance for interpretation of MCT results.

Direct fitness for dynamic kin selection.

The direct-fitness approach to modelling the evolution of social traits is an alternative to the classical inclusive-fitness-based approach. Despite both its utility and popularity, the direct-fitness approach has not yet been extended to include the analysis of dynamic traits, i.e. traits whose level of expression may vary over time. In this article, I apply the direct-fitness approach to cope with the evolution of a dynamic resource-allocation behaviour when this behaviour influences the fitness of relatives. I am able to implement the direct-fitness approach using components (reproductive value, fitness changes and measures of relatedness) found in standard, social-evolutionary models. I illustrate the modified direct-fitness model with an example studied by previous authors, and I show how the direct-fitness perspective can aid the validation of analytical results by means of a genetic algorithm.

The genetical theory of kin selection.

Natural selection operates both directly, via the impact of a trait upon the individual's own fitness, and indirectly, via the impact of the trait upon the fitness of the individual's genetically related social partners. These effects are often framed in terms of Hamilton's rule, rb - c > 0, which provides the central result of social-evolution theory. However, a number of studies have questioned the generality of Hamilton's rule, suggesting that it requires restrictive assumptions. Here, we use Fisher's genetical paradigm to demonstrate the generality of Hamilton's rule and to clarify links between different studies. We show that confusion has arisen owing to researchers misidentifying model parameters with the b and c terms in Hamilton's rule, and misidentifying measures of genotypic similarity or genealogical relationship with the coefficient of genetic relatedness, r. More generally, we emphasize the need to distinguish between general kin-selection theory that forms the foundations of social evolution, and streamlined kin-selection methodology that is used to solve specific problems.

Assessing adherence to objective disease monitoring and outcomes with adalimumab in a real-world IBD cohort.

BACKGROUND: Data suggests that tight objective monitoring may improve clinical outcomes in IBD. AIM: To assess the adherence to serial tight objective monitoring(clinical and biomarkers) and its effect on clinical outcomes. METHODS: We retrospectively reviewed the chart of 428 consecutive IBD patients started on adalimumab between January 1,2015-January 1,2019 [338 Crohn's disease(CD), 90 ulcerative colitis(UC)]. Clinical symptoms(assessed by Harvey-Bradshaw-Index,partial Mayo),C-Reactive Protein(CRP), and fecal calprotectin(FCAL) assessments were captured at treatment initiation and at 3,6,9, and12 months. Dose optimization and drug sustainability curves were plotted by Kaplan-Meier method. RESULTS: Clinical evaluation was available in nearly all patients at 3(CD-UC:95-94%), 6(90-83%), 9(86-85%) and 12(96-89%) months. CRP testing frequency decreased in CD patients over time. Compliance to serial FCAL testing was low. Clinical remission at one-year was higher in patients adherent to early assessment visit at 3 months(p = 0.001 for CD and UC). Adherence to early follow-up resulted in earlier dose optimization in CD and UC patients(pLogrank=0.026 for UC & p = 0.09 for CD). Overall drug sustainability did not differ. CONCLUSION: Clinical & CRP, but not FCAL, were frequently assessed in patients starting adalimumab. Adherence to early objective combined follow-up visits resulted in earlier dose optimization, improved one-year clinical outcomes but did not change drug sustainability.

Investment in the public good through conditional phenotypes of large effect.

We investigate the evolution of an individual's willingness to invest in a public good (what we call, helping) in a patch-structured population with limited natal dispersal. We assume that an individual's decision to invest is informed by its dispersal status: an individual makes one decision given it is native to the patch on which it breeds, and is free to make a different decision given that it is not native to the patch on which it breeds. Unlike previous work, we assume that investment in the public good, and the public good, itself, both have a large effect on individual fecundity. Kin selection analysis reveals that only extreme investment decisions (i.e. 'always invest' or 'never invest') can be evolutionarily stable. Numerical results suggest that the evolutionary instability of the 'never invest' phenotype (what we call, complete nonhelping) implies the evolutionary stability of 'always invest' (what we call, complete helping). In addition, numerical results show that bistability of extreme phenotypes is possible, indicating that the adaptive significance of altruism, in this context, is greater than has been previously recognized. Numerical results are supported by computer simulation, and results, themselves, are briefly discussed in a concluding section.

Predicting relapse in Crohn's disease: a biopsychosocial model.

BACKGROUND: Crohn's disease (CD) is a chronic relapsing inflammatory bowel disorder. Both biological and psychosocial factors may modulate the illness experience. AIM: The aim of this study was to identify clinical, biological and psychosocial parameters as predictors of clinical relapse in quiescent CD. METHODS: Patients in medically induced remission were followed prospectively for 1 year, or less if they relapsed. Disease characteristics were determined at baseline. Serum cytokines, anti-Saccharomyces cerevisiae antibodies, C-reactive protein (CRP), erythrocyte sedimentation rate and intestinal permeability were measured every 3 months. Psychological distress, perceived stress, minor life stressors and coping strategies were measured monthly. A time-dependent multivariate Cox regression model determined predictors of time to relapse. RESULTS: 101 patients (60 females, 41 males) were recruited. Fourteen withdrew and 37 relapsed. CRP (HR = 1.5 per 10 mg/l, 95% CI 1.1 to 1.9, p = 0.007), fistulising disease (HR = 3.2, 95% CI, 1.1 to 9.4, p = 0.04), colitis (HR = 3.5 95% CI 1.2 to 9.9, p = 0.02) and the interaction between perceived stress and avoidance coping (HR = 7.0 per 5 unit increase for both scales, 95% CI 2.3 to 21.8, p = 0.003) were predictors of earlier relapse. CONCLUSIONS: In quiescent CD, a higher CRP, fistulising disease behaviour and disease confined to the colon were independent predictors of relapse. Moreover, patients under conditions of low stress and who scored low on avoidance coping (ie, did not engage in social diversion or distraction) were least likely to relapse. This study supports a biopsychosocial model of CD exacerbation.

Fixation probabilities when generation times are variable: the burst death model.

Estimating the fixation probability of a beneficial mutation has a rich history in theoretical population genetics. Typically, to attain mathematical tractability, we assume that generation times are fixed, while the number of offspring per individual is stochastic. However, fixation probabilities are extremely sensitive to these assumptions regarding life history. In this article, we compute the fixation probability for a "burst-death" life-history model. The model assumes that generation times are exponentially distributed, but the number of offspring per individual is constant. We estimate the fixation probability for populations of constant size and for populations that grow exponentially between periodic population bottlenecks. We find that the fixation probability is, in general, substantially lower in the burst-death model than in classical models. We also note striking qualitative differences between the fates of beneficial mutations that increase burst size and mutations that increase the burst rate. In particular, once the burst size is sufficiently large relative to the wild type, the burst-death model predicts that fixation probability depends only on burst rate.

Severe insulin resistance secondary to insulin antibodies: successful treatment with the immunosuppressant MMF.

We have evaluated the use of the immunosuppressant mycophenolate mofetil (MMF) in the treatment of severe insulin resistance caused by neutralising anti-insulin antibodies in type 1 diabetes mellitus (T1DM). A 12-yr-old boy with a 5-month history of T1DM developed severe immunological insulin resistance secondary to human insulin antibodies. Various different treatment modalities, including lispro insulin, intravenous insulin, prednisolone and immunoabsorption, were tried, all without a sustained response to treatment. Although the introduction of the immunosuppressant MMF only resulted in a small reduction in haemoglobin A1c (from 10.9 to 9.8%), it did result in a significant reduction in insulin requirements from 6000 to 250 U/d (75 to 3.1 U/kg/d), disappearance of the severe nocturnal hypoglycaemia associated with high titres of insulin antibodies and a reduction in the level of these antibodies from 34.6 to 2.7 mg/dL. MMF may be considered as a means of immunosuppression in patients with markedly raised insulin antibodies whose diabetes cannot be controlled with insulin alone.

Phytophotodermatitis after gardening.

Phytophotodermatitis, otherwise known as 'Strimmer's Rash' is an unusual cause of a widespread rash. We present a case of phytophotodermatitis, which was initially misdiagnosed as chickenpox; the correct diagnosis was made after further careful history taking and illustrates the importance of taking a thorough history when presented with what appears to be a spot diagnosis.

Vertebral wedge fracture after speedboat 'splash down'.

A case is presented of a soldier with wedge fracture of T12 sustained after an axial compression (+/- flexion) injury in a Rigid-Hull Inflatable Boat (RIB). Very powerful boats, such as RIBs, are used on a daily basis in the Royal Navy (RN). Despite this, fractures of the spine are unusual (1). This study explores the mechanism of injury and illustrates that a wedge fracture should be considered in anyone presenting with back pain after a 'splash down' injury.

Cutaneous myiasis with Dermatobia hominis (human bot fly) larvae treated both conservatively and surgically.

A case is presented of infestation with the larvae of Dermatobia hominis (human bot fly). This case is unusual in that it provides an example of three different outcomes for separate lesions in the same patient; spontaneous resolution, conservative treatment and surgical intervention. It also illustrates that myiasis should be included in the differential diagnosis of any skin lesion of a patient returning from the tropics.

Do serum levels of eosinophil granule-derived protein change in patients undergoing pelvic radiotherapy?

AIMS: Eosinophils have an important role in the pathogenesis of inflammatory bowel disease, with faecal levels of the eosinophil granule proteins, eosinophil cationic protein (ECP) and eosinophil protein X (EPX) reflecting disease activity. Eosinophil crypt abscesses are a characteristic histological finding in acute gastrointestinal radiation-induced mucosal damage. This pilot study aimed to investigate changes in serum levels of ECP/EPX during pelvic radiotherapy. MATERIALS AND METHODS: Patients with no history of inflammatory bowel disease, starting a 5-week course of pelvic radiotherapy, had serum ECP/EPX levels measured before radiotherapy and during the fourth week of treatment. Bowel toxicity was graded at week 4 using the Common Toxicity Criteria Scale. RESULTS: Fifteen patients who were to undergo adjuvant radiotherapy for gynaecological cancer were recruited. The mean serum levels of ECP and EPX before treatment were 17.3 microg/l (range 2.0-49.3 microg/l) and 37.3 microg/l (range 12.0-94.0 microg/l), respectively. The mean serum levels during week 4 of radiotherapy for ECP and EPX were 43.0 microg/l (range 2.4-164.0 microg/l) and 38.7 microg/l (range 9.0-79.0 microg/l), respectively. Serum ECP levels increased at week 4 compared with levels before radiotherapy (P = 0.02). Acute bowel toxicity was seen in 12 patients (80%) at week 4: Grade 1 in 25% patients and Grade 2 in 75%. In this small study, no correlation was seen between acute bowel toxicity at week 4 and serum ECP or EPX levels. CONCLUSIONS: Serum ECP levels increase in response to pelvic irradiation. This may reflect the known involvement of eosinophils in the acute response to radiotherapy. Further study is required to determine when levels start to rise and their relationship to the degree of acute bowel toxicity.

Polymorphic keratins in human epidermis.

Human epidermal keratins from many different individuals were identified and compared by both high-resolution 1- and 2-dimensional gel electrophoresis and immunoblotting. While the polypeptide patterns obtained for keratin-enriched cytoskeletal preparations could be considered typical of normal interfollicular epidermis, they also disclosed variations, among the individuals, concerning some of the constituent protein subunits. Three sets of interindividually varying keratins could be distinguished owing to their distinct, though small, differences in electrophoretic mobility on sodium dodecyl sulfate-polyacrylamide gels and their similar or identical charge characteristics upon nonequilibrium pH gradient electrophoresis: the basic keratins 1a and 1b as well as 5a and 5b and the acidic keratins 10a and 10b. Of each set either a doublet, showing a marked 1:1 ratio of polypeptides, or the one or the other variant protein was detected together with keratin 14, which did not display any variation in a series of 148 individual tissue samples tested. Thus, the keratin composition of human epidermis could be summarized in the formula: (1a v 1b) + (5a v 5b) + (10a v 10b) + 14. The systematic appearance of the variants suggested that each protein within a set is the product of an independent allele. In support of this hypothesis we have found that the same variant is expressed in other epithelia of a given individual. Moreover, the frequency of any of the keratins in our sampling concurred with the frequency predicted by the Hardy-Weinberg relation for the distribution of alleles in a population, as did the frequency distribution of particular keratin patterns.

Specificity of indexes of malnutrition when applied to apparently healthy people: the effect of age.

Protein-energy malnutrition is thought to be widespread in hospitalized patients. However, the specificity of indexes used to assess malnutrition is uncertain. We therefore assessed the rate of false-positive diagnoses of malnutrition when biochemical-anthropometric indexes were applied to healthy subjects. Nutritional status was assessed in 175 healthy blood donors (aged 44.2 +/- 13.4 y) and in 34 highly fit elderly volunteers (aged 74.7 +/- 3.6 y) participating in the Nijmegen Four Days Walking March. We investigated both the Nutritional Risk Index [(1.489 x albumin) + (41.7 x present/usual weight)] and the Maastricht Index [20.68-(0.24 x albumin, g/L)-(19.21 x serum transthyretin, g/L)-(1.86 x lymphocytes, 10(6)/L)-(0.04 x ideal weight)]. We found previously that 52-64% of nonsurgical hospitalized patients were malnourished according to these indexes. In the present study, 1.9% of the 209 volunteers had apparent malnutrition according to the Nutritional Risk Index and 3.8% according to the Maastricht Index. The prevalence of apparent malnutrition in the elderly volunteers was 5.9% and 20.6%, respectively. The rate of false-positive diagnoses was acceptably low in those aged < 70 y with both the Nutritional Risk Index and the Maastricht Index; therefore, the use of these indexes will not cause a clinically significant increase in the prevalence of malnutrition because patients who are not malnourished are included. The high percentage of spurious malnutrition in the elderly limits the use of the Maastricht Index to subjects aged < 70 y.