The dynamics of parent-offspring relationships in mammals

Evolutionary theories about parent-offspring relationships have predicted that young will aggressively demand food and care from their parents at the time of weaning - when the parents should, in their own interests, reserve their efforts for future offspring. Detailed studies of the behavioural development of mammals have given only limited support for these expectations. Often the mother is more amenable to the needs of her offspring than evolutionary theory predicts, and often offspring are sensitive to the state of their mother, tuning the pattern of their own development accordingly. Such aggression as is seen between mother and offspring tends to occur at stages other than weaning. The mismatch between theory and evidence may arise because a mother needs to monitor her offspring's state as well as her own and respond appropriately in order to maximize her own reproductive success. Similarly, an offspring needs to monitor its mother and prepare for the world in which it will grow up, in order to maximize its chances of surviving to breed.     

Early springs and breeding performance in two sympatric duck species with different migration strategies

The capacity of migratory species to adapt to climate change may depend on their migratory and reproductive strategies. For example, reproductive output is likely to be influenced by how well migration and nesting are timed to temporal patterns of food abundance, or by temperature variations during the brood rearing phase. Based on two decades (1988–2009) of waterfowl counts from a boreal catchment in southern Finland we assessed how variation in ice break‐up date affected nesting phenology and breeding success in two sympatric duck species, Mallard Anas platyrhynchos and Eurasian Teal Anas crecca. In Fennoscandia these species have similar breeding habitat requirements but differ in migration distance; Teal migrate roughly seven times as far as do Mallard. Annual ice break‐up date was used as a proxy of spring ‘earliness’ to test the potential effect of climate change on hatching timing and breeding performance. Both species were capable of adapting their nesting phenology, and bred earlier in years when spring was early. However, the interval from ice break‐up to hatching tended to be longer in early springs in both species, so that broods hatched relatively later than in late springs. Ice break‐up date did not appear to influence annual number of broods per pair or annual mean brood size in either species. Our study therefore does not suggest that breeding performance in Teal and Mallard is negatively affected by advancement of ice break‐up at the population level. However, both species showed a within‐season decline in brood size with increasing interval between ice break‐up and hatching. Our study therefore highlights a disparity between individuals in their capacity to adjust to ice break‐up date, late breeders having a lower breeding success than early breeders. We speculate that breeding success of both species may therefore decline should a consistent trend towards earlier springs occur.     

Some experience in an area health authority child health clinic.

Three years'' experience as a doctor taking two clinics a week in an area health authority child health clinic was reviewed. A wide range of clinical conditions was seen, including: problems associated with feeding in breast- and bottle-fed infants; minor developmental abnormalities (mental, behavioural, and physical); surgical and orthopaedic conditions requiring treatment; medical conditions, mainly respiratory and alimentary infections, skin conditions, and problems of over-treatment for minor ailments; and minor genetic abnormalities. Mothers asked for advice on a wide range of topics, risks and benefits of immunisation being the most common. The clinic doctor needs a wide experience in paediatrics to deal with such problems. It is suggested that all lecturers in child health and paediatric and senior registrars should take one clinic a week for six months, and all medical students should attend some clinics as part of their paediatric training. Health visitors have an important role in helping the clinic doctor, but their training should be more realistic and appropriate facilities should be provided to keep them up to date in their work.     

The analysis of mortality by the subject-years method

The observed mortality of a group of individuals often needs to be compared with that expected from the death rates of the national population, with allowance made for age and period. Expected deaths are usually calculated by the subject-years method (Case and Lea, 1955, British Journal of Preventive and Social Medicine 9, 62-72), in which each person is assumed at risk up to the date of the analysis, the date of death, or the date the person was lost to follow-up, whichever is first. Some of the properties of this method are described, including an approach based on likelihood. For this purpose the observed number of deaths may be treated as though it were a Poisson variable. The likelihood approach leads to a generalization to the cases where the groups have a factorial structure or where covariates are available for each individual. The calculations are readily carried out by use of GLIM or GENSTAT.     

Hatching date vs laying date: what should we look at to study avian optimal timing of reproduction?

Most research conducted on optimal timing of reproduction in birds has traditionally considered laying date of the first egg as the event that needs to be related to the time of maximum food availability. However, what (most) birds need to time with the seasonal peak of food availability is the moment of maximum food demand of their nestlings, which is more tightly related with hatching date than with laying date. After initiating egg laying, birds still have some opportunities to adjust the time of highest food demand, as during the several days elapsed between laying of the first egg until hatching, more precise cues will become available to birds in order to make a more accurate match with food availability. I provide an overview of the suite of mechanisms available to birds for shortening or enlarging the interval between laying and hatching date, which include laying gaps, adjustment of clutch size, variation in onset and intensity of incubation, and differential investment on eggs. Then I illustrate with an example the extent to which birds can adjust hatching dates after egg laying. I argue that birds should more accurately time hatching date rather than laying date to maximum food availability on the basis of available cues. Therefore, I suggest that researchers should target on hatching date rather than laying date to better study optimal timing of reproduction in birds. Exploration of responses other than adjusting laying date to changing environmental conditions will surely uncover key aspects of avian reproductive biology and behaviour that have been ignored until now. This is a necessary step towards a better understanding of capacities of organisms to adapt to a changing world in particular, and of fitness consequences of timing of reproduction in general.     

Delayed oviposition: a female strategy to counter infanticide by males?

Conflicts of interest between males and females can lead toan evolutionary arms race in which adaptations of each sex coevolve.Intersexual conflict is extreme in the brood caring, semelparousspider Stegodyphus lineatus; males encountering females thathave already produced their usually single egg sac attempt toremove and discard the egg sac and then remate with the female. Femalesthat cannot defend their eggs lose valuable time and fecundityby having to replace the clutch. Selection should favor femalesthat complete their suicidal maternal care as quickly as possiblebecause of the high risk of predation. However, some femalestake up to four times longer to oviposit than others. I proposethat females minimize the risk of male infanticide by postponingoviposition. Accordingly, early-maturing females, who sufferthe highest risk of infanticide by males, should have a longerinterval between maturation and oviposition than late-maturingfemales. The date of maturation significantly predicted theinterval between maturation and oviposition and explained upto 35% of its variation in a data set from a natural population andlonger term data from a seminatural, enclosed population. Bodysize was predicted to have a weak effect on the timing of ovipositionand was consistently less important than maturation date. Theobserved facultative timing of oviposition may have evolvedas a result of intersexual conflict over mating.     

The EU medical device regulation: Implications for artificial intelligence-based medical device software in medical physics

Medical device manufacturers are increasingly applying artificial intelligence (AI) to innovate their products and to improve patient outcomes. Health institutions are also developing their own algorithms, to address specific needs for which no commercial product exists.Although AI-based algorithms offer good prospects for improving patient outcomes, their wide adoption in clinical practice is still limited. The most significant barriers to the trust required for wider implementation are safety and clinical performance assurance .Qualified medical physicist experts (MPEs) play a key role in safety and performance assessment of such tools, before and during integration in clinical practice. As AI methods drive clinical decision-making, their quality should be assured and tested. Occasionally, an MPE may be also involved in the in-house development of such an AI algorithm. It is therefore important for MPEs to be well informed about the current regulatory framework for Medical Devices.The new European Medical Device Regulation (EU MDR), with date of application set for 26 of May 2021, imposes stringent requirements that need to be met before such tools can be applied in clinical practice.The objective of this paper is to give MPEs perspective on how the EU MDR affects the development of AI-based medical device software. We present our perspective regarding how to implement a regulatory roadmap, from early-stage consideration through design and development, regulatory submission, and post-market surveillance. We have further included an explanation of how to set up a compliant quality management system to ensure reliable and consistent product quality, safety, and performance .     

Thyroid Hormone Deposition in Avian Eggs and Effects on Embryonic Development

Studies to date indicate that thyroid hormones are present inthe eggs of chickens and quail and that those hormones are primarilyin the yolk. Quail hens deposit thyroid hormones into eggs inproportion to their own thyroid status, but appear to show someregulation of this process. Indirect studies suggest that thyroidhormones are transferred into oocytes bound to lipoproteinsand transthyretin, both of which are taken up by receptor-mediatedprocesses. Thyroid hormones bound to yolk lipoproteins may enterembryos with yolk that is taken up by non-specific endocytosisor they may be transported into the embryo by specific carriers.To date most of these ideas about thyroid hormone transportinto egg yolk and from egg yolk into embryos have not been investigateddirectly. In quail, very high T₄ content of eggs is associatedwith accelerated differentiation and growth of embryonic pelviccartilage, a thyroid hormone-responsive tissue. We evaluatethese effects on embryonic tissues and the changes in yolk hormonecontent during incubation in relation to the timing of thyroiddevelopment and studies of the capability for tissue responsesto thyroid hormones during early embryonic life     

Biosimilars 2.0

In the European Union, biosimilar products have been approved since 2006 under an abbreviated pathway that leverages their similarity to an existing “reference” biological product. The products approved to date are based on recombinant versions of endogenous proteins with well-understood structures and pharmacology, but complicated safety and immunogenicity profiles. The period during the 2000s that included the first reviews, approvals, sale and use of biosimilars, is referred to herein as “Biosimilars 1.0.” Over the next several years, a new and advanced tranche of biosimilars will be developed for complex reference products, including medicines used in the treatment of cancer and autoimmune diseases. A global market for biosimilars is developing, and this may well foreshadow the beginning of the second era of product development. This Biosimilars 2.0 period will likely be characterized by the development of complex products, global harmonization of standards, and the increasing demand for long-term monitoring of pharmaceuticals. The products developed in this period should exhibit high levels of fidelity to the reference products and should be rigorously evaluated in analytical, non-clinical and clinical comparisons. Additionally, Biosimilars 2.0 manufacturers should strive for transparency in their labels and take proactive strides to be accountable to providers and patients for the quality of their products. An important opportunity now exists for the healthcare community, industry and regulators to work in partnership to outline the appropriate standards for these products to facilitate increased access while meeting patients’ needs.     

The cheek plumage patch is an amplifier of dominance in great tits

Amplifiers are signals that enhance the perception of other signals or cues, but no studies to date provide empirical evidence for the role of these signals in a reproductive context. Here we use the white cheek patch of great tits as a model for studying this issue. Aggressive interactions decrease patch immaculateness, so patch size may be an amplifier of dominance, that is, more clearly reveal status. If so, in high-quality individuals patch size should correlate positively with reproductive success (here estimated by laying date, assuming that the earlier the better), whereas low-quality individuals with a large patch should only more clearly reveal their low quality and thus suffer low reproductive success, which is exactly the pattern found in males. In contrast, the cheek patch does not seem to function as an amplifier in female great tits.     

Mechanisms in macroecology: AWOL or purloined letter? Towards a pragmatic view of mechanism

Ecologists often believe the discovery of mechanism to be the central goal of scientific research. While many macroecologists have inherited this view, to date they have been much more efficient at producing patterns than identifying their underlying processes. We discuss several possible attitudes for macroecologists to adopt in this context while also arguing that in fact macroecology already has many mechanisms that are ignored. We briefly describe six of these: central limit theorem, fractals, random sampling and placement, neutral theory (and descendents), concordance of forces, and maximum entropy. We explore why these mechanisms are overlooked and discuss whether they should be. We conclude that macroecology needs to take a more pragmatic, less ideological approach to mechanism. We apply this viewpoint to the recent controversy over maximum entropy and suggest that maximum entropy needs to be viewed more pragmatically and less ideologically.     

Role of intrinsic disorder in transient interactions of hub proteins

Hubs in the protein-protein interaction network have been classified as "party" hubs, which are highly correlated in their mRNA expression with their partners while "date" hubs show lesser correlation. In this study, we explored the role of intrinsic disorder in date and party hub interactions. The data reveals that intrinsic disorder is significantly enriched in date hub proteins when compared with party hub proteins. Intrinsic disorder has been largely implicated in transient binding interactions. The disorder to order transition, which occurs during binding interactions in disordered regions, renders the interaction highly reversible while maintaining the high specificity. The enrichment of intrinsic disorder in date hubs may facilitate transient interactions, which might be required for date hubs to interact with different partners at different times.     

Effects of long-term implanted data loggers on macaroni penguins Eudyptes chrysolophus

We tested the hypothesis that implanted data loggers have no effect on the survival, breeding success and behaviour of macaroni penguins Eudyptes chrysolophus . Seventy penguins were implanted with heart rate data loggers (DLs) for periods of up to 15 months. When compared to control groups, implanted penguins showed no significant difference in over-wintering survival rates, arrival date and mass at the beginning of the breeding season. Later in the breeding season, implanted penguins showed no significant difference in the duration of their incubation foraging trip, breeding success, fledging mass of their chicks, date of arrival to moult and mass at the beginning of the moult fast. We conclude that implanted devices had no effects on the behaviour, breeding success and survival of this species. We contrast these results to those from studies using externally attached devices, which commonly affect the behaviour of penguins. We suggest that implanted devices should be considered as an alternative to externally attached devices in order to obtain the most accurate representation of the free-ranging behaviour, ecology and physiology of penguins.     

Dynamics based alignment of proteins: an alternative approach to quantify dynamic similarity

Background  

The dynamic motions of many proteins are central to their function. It therefore follows that the dynamic requirements of a protein are evolutionary constrained. In order to assess and quantify this, one needs to compare the dynamic motions of different proteins. Comparing the dynamics of distinct proteins may also provide insight into how protein motions are modified by variations in sequence and, consequently, by structure. The optimal way of comparing complex molecular motions is, however, far from trivial. The majority of comparative molecular dynamics studies performed to date relied upon prior sequence or structural alignment to define which residues were equivalent in 3-dimensional space.     

Sex allocation in black-capped chickadees Poecile atricapilla

Optimal sex allocation for individuals can be predicted from a number of different hypotheses. Fisherian models of sex allocation predict equal investment in males and females up to the end of parental care and predict brood compositions based on the relative costs of producing males and females. The Trivers-Willard hypothesis predicts that individual females should alter the sex ratio of their broods based on their own condition if it has a differential impact on the lifetime reproductive success of their sons and daughters. The Charnov model of sex allocation predicts that females should alter sex allocation based on paternal attributes that may differentially benefit sons versus daughters. Because females are the heterogametic sex in birds, many recent studies have focussed on primary sex ratio biases. In black-capped chickadees Poecile atricapilla , males are larger than females suggesting they may be more costly to raise than females. Female condition affects competitive ability in contests for mates, and thus may be related to variance in fecundity. Females prefer high-ranking males as both social and extrapair partners. These observations suggest that females might vary the sex ratio of their broods based on the predictions of any of the above models. Here, we report on the results of PCR based sex determination of 1093 nestlings in 175 broods sampled from 1992 to 2001. Population-wide, we found a mean brood sex ratio of 0.525±0.016, with no significant deviation from a predicted binomial distribution. We found no effect of clutch size, female condition, hatch date, parental rank or paternity. Our results reject the idea that female black-capped chickadees systematically vary sex allocation in their broods.     

Medical professionalism and the social contract

Conceptions of professionalism in medicine draw on social contract theory; its strengths and weaknesses play out in how we reason about professionalism. The social contract metaphor may be a heuristic device prompting reflection on social responsibility, and as such is appealing: it encourages reasoning about privilege and responsibility, the broader context and consequences of action, and diverse perspectives on medical practice. However, when this metaphor is elevated to the status of a theory, it has well-known limits: the assumed subject position of contractors engenders blind spots about privilege, not critical reflection; its tendency to dress up the status quo in the trappings of a theoretical agreement may limit social negotiation; its attempted reconciliation of social obligation and self-interest fosters the view that ethics and self-interest should coincide; it sets up false expectations by identifying appearance and reality in morality; and its construal of prima facie duties as conditional misdirects ethical attention in particular situations from current needs to supposed past agreements or reciprocities. Using philosophical ideas as heuristic devices in medical ethics is inevitable, but we should be conscious of their limitations. When they limit the ethical scope of debate, we should seek new metaphors.     

c-erbB-2 expression in primary breast cancer.

c-erbB-2 is an oncoprotein which is overexpressed in up to 40% of primary breast cancers. c-erbB-2 overexpression is a bad prognostic factor in patients with lymph node-positive disease. Unfortunately, there has been no agreement to date on whether c-erbB-2 overexpression is of prognostic significance in patients with lymph node-negative disease. c-erbB-2 overexpression is correlated with the absence of estrogen receptor expression in a number of publications. Correlation between c-erbB-2 overexpression and hormone sensitivity in the clinical setting is less well established and is the focus of ongoing studies. Both preclinical and clinical studies support an association between c-erbB-2 receptor overexpression and resistance to alkylating agents. In contrast, the data for c-erbB-2 and anthracyclines should be viewed in a slightly different manner. Anthracyclines appear to have a greater therapeutic effect in c-erbB-2-positive disease which may be dose sensitive. In c-erbB-2-negative disease not only is the therapeutic effect reduced but there does not appear to be any improved response to higher doses of anthracyclines. The data for c-erbB-2 and the taxanes is still not clear enough to provide any definite conclusions. If there is a correlation it would at present appear to be between paclitaxel and response rates, but this needs to be confirmed in larger studies. Few studies have looked at changes in c-erbB-2 on therapy. Those that have seem to show no significant change on either tamoxifen or chemotherapy.     

Primary care development zones.

Most commentators on the Tomlinson report have agreed with its emphasis on improving primary and community care. The three elements of such a strategy are a remedial programme to bring primary care up to national standards, a programme to provide such services to people with non-standard needs such as mobile Londoners, ethnic minorities, and homeless people, and the development of an expanded model of primary care. No one model will be appropriate across all of London. The process should start with an audit of existing resources and services within each community, together with an analysis of needs. From this would develop a local programme with specific plans for investment in premises, staffing, training, and management. New contractual mechanisms may be needed to attract practitioners, improve their premises, secure out of hours services, and provide medical cover for community beds. There should also be incentives for closer working between primary and secondary services. No developments on the scale needed for London have been carried out in primary care within the lifetime of the NHS--but their success will be critical to the calibre of health services for Londoners into the next century.