Carry-over effects of seasonal migration on reproductive success through breeding site retention in a partially migratory bird.

Understanding the maintenance and dynamics of phenotypic polymorphisms requires unpicking key ecological mechanisms shaping the fitness costs and benefits of expressing alternative phenotypes, generating selection. Seasonal migration versus year-round residence expressed in partially migratory populations represents one common polymorphism that can experience strong selection through differential reproductive success. Yet, key hypothesised pathways that could generate such selection remain to be empirically tested. One hypothesis is that migratory tactics affect subsequent reproductive success through carry-over effects on breeding site retention and resulting breeding dispersal. By remaining in breeding areas all year round, residents could retain their preferred breeding site between years, and consequently have higher reproductive success. Conversely, migrants that escape harsh non-breeding season conditions could return in better condition, with high resource holding potential, and outcompete residents to retain their site. Such effects could further depend on migration timing and vary between years. Yet, such pathways have not been quantified, precluding empirical parameterisation of partial migration theory. We used 4 years of breeding and non-breeding season data from partially migratory European shags (Gulosus aristotelis) to test whether the three most frequent migratory tactics in this population (full resident, early migrant departing soon after breeding, and late migrant departing in late autumn) differed in their breeding site retention; whether site retention predicted reproductive success; and hence whether effects of migratory tactic on reproductive success were explicable through site retention. Overall, residents were much more likely to retain their breeding site between years than both early and late migrants, and site retention was associated with increased reproductive success. Yet, these effects varied somewhat among years: late migrants were always least likely to retain their site but had variable relative reproductive success. Path analyses revealed that effects of migratory tactic on reproductive success were only partly attributable to breeding site retention. These results indicate that multiple mechanisms underlie reproductive selection on migratory tactics, potentially contributing to maintaining behavioural polymorphisms. Yet, the clear associations between migratory tactics and local breeding dispersal reveal that these movements can be strongly interlinked across seasons, shaping overall spatioseasonal dynamics in partially migratory systems.

A fit-for-purpose copper speciation method for the determination of exchangeable copper relevant to Wilson's disease.

Exchangeable copper (CuEXC), mainly comprised copper (Cu) bound to albumin, has been proposed as a specific marker of Cu overload in Wilson's disease (WD). To the author's knowledge, there are no methods capable of determining reliably CuEXC to meet the requirements and challenges faced by a clinical trial. The present work describes a novel speciation strategy for the determination of the main Cu-species in human serum by anion-exchange high-performance liquid chromatography coupled to inductively coupled plasma mass spectrometry (HPLC-ICP-MS). A label-free protein quantification approach was conducted where the concentration of Cu associated to the protein fraction was based on its relative peak area distribution and the total Cu concentration in the sample. Such a methodology was characterized in terms of selectivity, sensitivity, precision, and robustness. Due to the lack of speciated Cu-reference materials, protein recovery was assessed by comparison with that of species-specific (SS) isotope dilution (ID). For this, a double SS HPLC-ICP-IDMS method for Cu-albumin was developed and presented here for the first time. Three human sera (two frozen LGC8211 and ERM®-DA250a, and the lyophilised Seronorm™ Human) were analyzed using both the relative and ID quantification methods. The validated relative approach, with relative expanded uncertainties (k = 2) between 5.7 and 10.1% for Cu-albumin concentrations ranging from 112 to 455 µg kg-1 Cu, was found to be able to discriminate between healthy and WD populations in terms of Cu-albumin content. Also, using such methodology, underestimation of CuEXC by the classical EDTA/ultrafiltration method was demonstrated. The methodology developed in this work will be invaluable for quality control assessment and WD drug monitoring. This work describes a Cu-protein quantification approach for the determination of exchangeable Cu relevant to Wilson's Disease.

Additive genetic and environmental variation interact to shape the dynamics of seasonal migration in a wild bird population.

Dissecting joint micro-evolutionary and plastic responses to environmental perturbations requires quantifying interacting components of genetic and environmental variation underlying expression of key traits. This ambition is particularly challenging for phenotypically discrete traits where multiscale decompositions are required to reveal nonlinear transformations of underlying genetic and environmental variation into phenotypic variation, and when effects must be estimated from incomplete field observations. We devised a joint multistate capture-recapture and quantitative genetic animal model, and fitted this model to full-annual-cycle resighting data from partially-migratory European shags (${Gulosus~{}aristotelis}$) to estimate key components of genetic, environmental and phenotypic variance in the ecologically critical discrete trait of seasonal migration versus residence. We demonstrate non-negligible additive genetic variance in latent liability for migration, resulting in detectable micro-evolutionary responses following two episodes of strong survival selection. Further, liability-scale additive genetic effects interacted with substantial permanent individual and temporary environmental effects to generate complex nonadditive effects on expressed phenotypes, causing substantial intrinsic gene-by-environment interaction variance on the phenotypic scale. Our analyses therefore reveal how temporal dynamics of partial seasonal migration arise from combinations of instantaneous micro-evolution and within-individual phenotypic consistency, and highlight how intrinsic phenotypic plasticity could expose genetic variation underlying discrete traits to complex forms of selection.

Cold comfort: Arctic seabirds find refugia from climate change and potential competition in marginal ice zones and fjords.

Climate change alters species distributions by shifting their fundamental niche in space through time. Such effects may be exacerbated by increased inter-specific competition if climate alters species dominance where competitor ranges overlap. This study used census data, telemetry and stable isotopes to examine the population and foraging ecology of a pair of Arctic and temperate congeners across an extensive zone of sympatry in Iceland, where sea temperatures varied substantially. The abundance of Arctic Brünnich's guillemot Uria lomvia declined with sea temperature. Accessibility of refugia in cold water currents or fjords helped support higher numbers and reduce rates of population decline. Competition with temperate Common guillemots Uria aalge did not affect abundance, but similarities in foraging ecology were sufficient to cause competition when resources are limiting. Continued warming is likely to lead to further declines of Brünnich's guillemot, with implications for conservation status and ecosystem services.

Cauda equina syndrome: a review of the current clinical and medico-legal position.

Cauda equina syndrome (CES) is a rare condition with a disproportionately high medico-legal profile. It occurs most frequently following a large central lumbar disc herniation, prolapse or sequestration. Review of the literature indicates that around 50-70% of patients have urinary retention (CES-R) on presentation with 30-50% having an incomplete syndrome (CES-I). The latter group, especially if the history is less than a few days, usually requires emergency MRI to confirm the diagnosis followed by prompt decompression by a suitably experienced surgeon. Every effort should be made to avoid CES-I with its more favourable prognosis becoming CES-R while under medical supervision either before or after admission to hospital. The degree of urgency of early surgery in CES-R is still not in clear focus but it cannot be doubted that earliest decompression removes the mechanical and perhaps chemical factors which are the causes of progressive neurological damage. A full explanation and consent procedure prior to surgery is essential in order to reduce the likelihood of misunderstanding and litigation in the event of a persistent neurological deficit.

Comparison of the Pharmacokinetic Profiles of Trientine Tetrahydrochloride and Trientine Dihydrochloride in Healthy Subjects.

BACKGROUND AND OBJECTIVE: Wilson disease (WD) is an autosomal recessive inherited disorder of copper metabolism. Chelation of excessive copper is recommended but data on the pharmacokinetics of trientine are limited. The aim of this study was to compare the pharmacokinetics of a new trientine tetrahydrochloride formulation (TETA 4HCl) with those of an established trientine dihydrochloride (TETA 2HCl) salt. METHODS: A randomised single-centre crossover study to evaluate the pharmacokinetics, safety and tolerability of two different oral formulations of trientine (TETA 4HCl tablets vs TETA 2HCl capsules) in 23 healthy adult subjects receiving a single dose equivalent to 600 mg of trientine base was performed. RESULTS: Following oral administration, the median time to reach maximum plasma concentration (Tmax) was 2.00 h (TETA 4HCl) and 3.00 h (TETA 2HCl). The rate (maximum plasma concentration [Cmax]) and extent (area under the plasma concentration-time curve from time zero to infinity [AUC0-∞]) of absorption of the active moiety, trientine, were greater (by approximately 68% and 56%, respectively) for TETA 4HCl than for the TETA 2HCl formulation. The two formulations presented a similar terminal elimination rate (λz) and a similar terminal half-life (t½) for trientine. Differences between TETA 4HCl and TETA 2HCl in the levels of the two main mono- and diacetylated metabolites were less than seen for trientine. For both tested formulations, healthy male volunteers demonstrated higher trientine plasma levels but lower mono- and diacetylated metabolite levels compared with females, with no sex differences in terminal half-life (t½) observed. Single oral doses of both formulations were safe and well tolerated. CONCLUSIONS: Compared with an identical dose of a TETA 2HCl formulation, the TETA 4HCl formulation provided more rapid absorption of trientine and greater systemic exposure in healthy subjects. Clinical Trials Number EudraCT # 2015-002199-25.

Spinal stability is improved by inducing a lumbar lordosis in boys with Duchenne Muscular Dystrophy: a pilot study.

The development of scoliosis in boys with Duchenne Muscular Dystrophy (DMD) is a significant, morbid event in the progression of the disease caused by progressive spinal musculature weakness. As an alternative to muscle activity, the spine can also be stabilised by locking the articular facet joints, which is achieved when the body is supported on a seat tilted anteriorly using a 'wedge', of the kind commonly recommended for low back pain. We tested spinal stability when using a seat tilted 15 degrees anteriorly in eight boys with DMD, without significant scoliosis, by measuring the ability to support a lateral load applied to the thorax through a sling and hawser. All eight boys tolerated lateral loading better with wedged seating and were able to support an average additional load of 95 g per kilogram of body weight compared to normal seating. Lateral load bearing was improved in 10 normal control boys by an average of 40 g per kilogram of body weight. These encouraging pilot findings indicate that there is a need for further studies on the effectiveness of passive mechanical factors in spinal stabilisation to delay the development of scoliosis in boys with DMD.

The revised structure, total synthesis, and absolute configuration of streptophenazine A.

A total synthesis of both diastereomers of the originally proposed structure for streptophenazine A (1) has been achieved. However, both synthetic compounds are different from the natural product. Re-examination of NMR data reported for streptophenazine A and a concise total synthesis of both diastereomers of 17 (17a and 17b) led to the structural revision of streptophenazine A to 17b. Asymmetric synthesis of (-)-streptophenazine A was also conducted, and its absolute configuration was determined to be 1'S,2'R.