Can environmental conditions experienced in early life influence future generations?

The consequences of early developmental conditions for performance in later life are now subjected to convergent interest from many different biological sub-disciplines. However, striking data, largely from the biomedical literature, show that environmental effects experienced even before conception can be transmissible to subsequent generations. Here, we review the growing evidence from natural systems for these cross-generational effects of early life conditions, showing that they can be generated by diverse environmental stressors, affect offspring in many ways and can be transmitted directly or indirectly by both parental lines for several generations. In doing so, we emphasize why early life might be so sensitive to the transmission of environmentally induced effects across generations. We also summarize recent theoretical advancements within the field of developmental plasticity, and discuss how parents might assemble different ‘internal’ and ‘external’ cues, even from the earliest stages of life, to instruct their investment decisions in offspring. In doing so, we provide a preliminary framework within the context of adaptive plasticity for understanding inter-generational phenomena that arise from early life conditions

Treating specific phobias in young people with autism and severe learning difficulties

Background: Animal phobias in young people with autism spectrum disorders and intellectual disability can impede access to the community and cause risky behaviours. Previous studies have suggested that CBT including systematic desensitization and modelling are effective for people with intellectual difficulties including those with comorbid autism. Methods of adapting treatment to people with little spoken language are not well described and the ethical issues concerning the young person and the animals during treatment have not been addressed. Aims: Using a case series of consecutive referrals to describe (1) adaptations to systematic desensitization when communication is impaired and (2) the ethics of involving animals in interventions. Method: Treatment planned was based on the use of systematic desensitization with a hierarchy of feared situations using visual symbols and schedules to communicate with the participants. Results: Five young people with autism, severe intellectual disabilities and minimal language were successfully treated for dog phobia. The adaptations included use of non-verbal means of communication such as printed symbols and activities such as jigsaw puzzles to present information in amore finely graded format. Conclusions: The treatment of specific animal phobias is possible with the use of minimal language provided that a variety of individualized stimuli approximating to the feared objects are developed and the safety of all participants is respected. Further work is required to develop sufficiently flexible treatment protocols, which in turn would enable a randomized controlled trial

Environmental change and the rate of phenotypic plasticity

With rapid and less predictable environmental change emerging as the ‘new norm’, understanding how individuals tolerate environmental stress via plastic, often reversible changes to the phenotype (i.e., reversible phenotypic plasticity, RPP), remains a key issue in ecology. Here, we examine the potential for better understanding how organisms overcome environmental challenges within their own lifetimes by scrutinizing a somewhat overlooked aspect of RPP, namely the rate at which it can occur. Although recent advances in the field provide indication of the aspects of environmental change where RPP rates may be of particular ecological relevance, we observe that current theoretical models do not consider the evolutionary potential of the rate of RPP. Whilst recent theory underscores the importance of environmental predictability in determining the slope of the evolved reaction norm for a given trait (i.e., how much plasticity can occur), a hitherto neglected possibility is that the rate of plasticity might be a more dynamic component of this relationship than previously assumed. If the rate of plasticity itself can evolve, as empirical evidence foreshadows, rates of plasticity may have the potential to alter the level predictability in the environment as perceived by the organism and thus influence the slope of the evolved reaction norm. However, optimality in the rate of phenotypic plasticity, its evolutionary dynamics in different environments and influence of constraints imposed by associated costs remain unexplored and may represent fruitful avenues of exploration in future theoretical and empirical treatments of the topic. We conclude by reviewing published studies of RPP rates, providing suggestions for improving the measurement of RPP rates, both in terms of experimental design and in the statistical quantification of this component of plasticity. acclimation, acclimation rate, acclimation time-course, phenotypic plasticity, plasticity rate, rapid environmental change, timescale of plasticitypublishedVersio

Maternal influences on offspring size, behaviour and energy metabolism

In my thesis I investigate the ecology of maternal influences: the unique ability of mothers to influence, via genetic and non-genetic means, the phenotypic expression of their offspring. My research is presented as a series of standalone chapters that are introduced and then summarised by a general introduction (Chapter 1) and a general discussion (Chapter 6) respectively. One of the main components of an organism’s energy budget is its baseline level of energy metabolism. Individual differences in this cost of self-maintenance (termed in this chapter, resting metabolic rate, RMR) are substantial, but the causes and consequences of this variation are obscure. In Chapter 2, I review the published literature and show that maternal influences (along with other factors) can contribute substantially to variation in offspring RMR. Also, the RMR - fitness relationship appears to be modulated by environmental conditions (e.g. food supply), suggesting that the fitness consequences of a given RMR may be context-dependent. Thus, I propose that broad-scale variation in RMR might persist in natural populations, due to both spatial and temporal variation in environmental conditions and the trans-generational influence of mothers. To further investigate maternal influences on offspring energy metabolism, I measured the standard metabolic rate (SMR, a measure equivalent to RMR but used in reference to ectothermic animals) of juvenile brown trout (Salmo trutta) in response to intra-clutch manipulations of egg cortisol and testosterone (Chapter 3). Although, neither hormone affected offspring SMR (egg testosterone treatment resulted in a likely pharmacological dose), juveniles from cortisol-treated eggs were smaller and subordinate to individuals from control eggs. This indicates that variation in the amount of cortisol deposited in eggs by females, either among clutches or within them, is likely to affect juvenile performance. In a separate experiment (Chapter 4), I investigated if within-clutch differences in the phenotypes of juvenile brown trout were systematically related to the position where each individual developed during oogenesis. For a given egg size, siblings from dominant mothers were initially larger (but had a lower mass-corrected SMR) if they developed in the rear of the egg mass. However, heterogeneity in the size of siblings from different positions in the egg mass diminished in lower ranking females. Juvenile social status also varied according to egg mass position, although the direction of this effect depended on their age. Maternal influences on offspring are not only determined by conditions experienced by females immediately prior to reproduction. In Chapter 5, I investigated whether the juvenile growth rate and adult reproductive traits of female wild Atlantic salmon are related to the performance of their offspring in the wild. Investment in egg size was linked to both the juvenile and adult phenotypes of mothers. Even when controlling for egg size, the influence of these ‘past’ and ‘present’ maternal traits extended to offspring performance. Offspring growth was positively related to maternal investment in reproduction and the juvenile growth rate of each mother. The survival and biomass of offspring were also linked to adult reproductive traits but these relationships differed for mothers that had grown at either fast or slow rates as juveniles. Overall my thesis demonstrates that maternal influences are a substantial source of variation in offspring size, behaviour and physiology, both among and within clutches. My research also underlines the importance of maternal influences for offspring ecology and therefore maternal fitness

Explaining symptoms after negative tests : towards a rational explanation

Peer reviewedPostprin

Real-world comorbidities and treatment patterns of patients with acromegaly in two large US health plan databases

Acromegaly is a rare, chronic, and debilitating disease that results from excessive growth hormone production. Clinically, this disease is associated with enlargement of soft tissue, excessive skeletal growth, and increased risk of cardiovascular disease. Acromegaly is often diagnosed late, when a wide range of comorbidities may already be present. First-line therapy for acromegaly is typically surgery; but a number of highly-specific pharmacological agents have recently enabled a more aggressive medical management of acromegaly. Since surgical cure of acromegaly is low for macroadenomas, medical control of active acromegaly is an important component of treatment. There are no published US data currently available regarding real-world rates of comorbidities and treatment patterns among patients with acromegaly. This retrospective study examined the comorbidities and treatment patterns of 949 health plan enrollees, who had acromegaly diagnosis and/or procedure codes in an administrative claims database from July 1, 2002 through June 30, 2010. Acromegaly was associated with high rates of hypertension and diabetes along with a number of other comorbidities. The incidence of comorbidities was highest among patients with acromegaly-related treatment, which may have resulted, in part, from inadequate disease management and/or poor disease control. Unexpectedly, 55 % of patients identified with acromegaly received no treatment for acromegaly (i.e., surgery, radiotherapy, and medication) and only 28 % received a medication treatment during the observation period. However, some patients may have received a curative surgery prior to the observation period, which may have reduced the use of other acromegaly-related treatments during the study period. Of those treated with medications, the most common first medications were octreotide, cabergoline, and bromocriptine. Given the high incidence of serious comorbidities associated with active acromegaly, earlier diagnosis and treatment, along with appropriate follow-up care, may potentially avoid the life-long consequences of uncontrolled disease