Effect of kelp gull harassment on southern right whale calf survival: a long-term capture-recapture analysis.

Kelp gulls (Larus dominicanus) commonly feed on the skin and blubber of surfacing southern right whales (SRW, Eubalaena australis) in the near shore waters of Península Valdés (PV), Argentina. Mothers and especially calves respond to gull attacks by changing their swimming speeds, resting postures and overall behaviour. Gull-inflicted wounds per calf have increased markedly since the mid-1990s. Unusually high mortality of young calves occurred locally after 2003, and increasing evidence points to gull harassment as a factor contributing to the excess deaths. After leaving PV, calves undertake a long migration with their mothers to summer feeding areas; their health during this strenuous exertion is likely to affect their probabilities of first-year survival. To explore the effects of gull-inflicted wounds on calf survival, we analysed 44 capture-recapture observations between 1974 and 2017, for 597 whales photo-identified in their years of birth between 1974 and 2011. We found a marked decrease in first-year survival associated with an increase in wound severity over time. Our analysis supports recent studies indicating that gull harassment at PV may impact SRW population dynamics.

Standardizing the surgical management of benign ovarian tumors in children and adolescents: A best practice Delphi consensus statement.

AIM: No widely agreed consensus protocols exist for the management of benign ovarian tumors (BOT) in children. This presents a substantial risk for suboptimal management. We aimed to generate multispecialty consensus guidance to standardize surgical management and provide a clear follow-up protocol for children with BOTs. METHODS: Prospective two-round confidential e-Delphi consensus survey distributed among multispecialty expert panel; concluded by two semistructured videoconferences. MAIN RESULTS: Consensus was generated on these core outcome sets: preoperative/intraoperative management; follow-up; adolescent gynecology referral. (1) Children with BOTs should receive the same management as other patients with potentially neoplastic lesions: Preoperative discussion at a pediatric oncology multidisciplinary meeting to risk stratify tumors, and management by health professionals with expertise in ovarian-sparing surgery and laparoscopy. (2) Ovarian-sparing surgery for BOTs should be performed wherever possible to maximize fertility preservation. (3) Ovarian masses detected during emergency laparoscopy/laparotomy should be left in situ wherever feasible and investigated appropriately (imaging/tumor markers) before resection. (4) Follow-up should be undertaken for all patients after BOT resection. Patients should be offered referral to adolescent gynecology to discuss fertility implications. CONCLUSION: This best practice Delphi consensus statement emphasizes the importance of managing children with BOTs through a well-defined oncological MDT strategy, in order to optimize risk stratification and allow fertility preservation by ovarian-sparing surgery wherever possible.

Incidence of Paediatric Stricturing Duodenal Crohn Disease: A 19-Year Population-based Cohort Study.

OBJECTIVES: Stricturing duodenal Crohn disease (CD) is a rare but serious presentation of CD causing significant morbidity. We aim to provide the first robust incidence data and case studies on this severe presentation in children. METHODS: A regional cohort of prospectively acquired incident cases of paediatric CD diagnosed <16 years of age in South-East Scotland was captured over a 19-year period (1999-2018). A retrospective review was conducted on the medical records of all patients together with a review of the available literature and consensus guidelines. Incidence rates for all CD and for duodenal stricturing CD were calculated. RESULTS: A total of 247 new cases of paediatric CD were diagnosed within the study period. Median age at diagnosis was 12.5 years with 62% male predominance. Overall paediatric CD incidence rate was 5.70/100,000/year with a specific duodenal B2 phenotype disease incidence rate of 0.05/100,000/year; representing 0.8% of incident cases at diagnosis. Two incident cases of stricturing duodenal CD presented with systemic symptoms of weight loss, abdominal pain, anorexia, and lethargy, together with persistent vomiting suggestive of obstruction. Both cases partially responded to intensive medical therapy but eventually required laparoscopic gastroduodenostomy. A detailed literature search confirmed there are no paediatric incidence data, guidelines, or case reports relating to duodenal stricture as either a presentation or complication of CD. CONCLUSIONS: Duodenal structuring disease is a rare but serious presentation of CD causing significant morbidity and not currently covered in the paediatric literature or consensus guidelines. Best practice medical and surgical management remain uncertain and require further research.

Minimally invasive surgery for superior mesenteric artery syndrome: a case report and literature review.

INTRODUCTION: Superior mesenteric artery syndrome is a rare condition characterised by nausea, vomiting, postprandial pain, anorexia and early satiety. Conservative management is tried initially, but if this fails, surgery is indicated. There are few reports in the literature concerning superior mesenteric artery syndrome in children, and fewer still managed surgically by minimally invasive means. CASE PRESENTATION: A 12-year-old girl presented with weight loss, early satiety and vomiting after corrective scoliosis surgery. After upper gastrointestinal endoscopy, contrast study and computed tomography imaging, a diagnosis of superior mesenteric artery syndrome was made. Conservative management by nasojejunal feeding failed; therefore, a laparoscopic duodeno-jejunostomy was undertaken. At follow-up, her symptoms had improved. CONCLUSION: This report describes the youngest child to undergo laparoscopic duodeno-jejunostomy for superior mesenteric artery syndrome. Laparoscopic duodeno-jejunostomy appears to be the most widely employed and reliable minimally invasive approach to superior mesenteric artery syndrome with a high success rate and acceptably low complication rate.

Predicting the effects of human developments on individual dolphins to understand potential long-term population consequences.

Human activities that impact wildlife do not necessarily remove individuals from populations. They may also change individual behaviour in ways that have sublethal effects. This has driven interest in developing analytical tools that predict the population consequences of short-term behavioural responses. In this study, we incorporate empirical information on the ecology of a population of bottlenose dolphins into an individual-based model that predicts how individuals' behavioural dynamics arise from their underlying motivational states, as well as their interaction with boat traffic and dredging activities. We simulate the potential effects of proposed coastal developments on this population and predict that the operational phase may affect animals' motivational states. For such results to be relevant for management, the effects on individuals' vital rates also need to be quantified. We investigate whether the relationship between an individual's exposure and the survival of its calves can be directly estimated using a Bayesian multi-stage model for calf survival. The results suggest that any effect on calf survival is probably small and that a significant relationship could only be detected in large, closely studied populations. Our work can be used to guide management decisions, accelerate the consenting process for coastal and offshore developments and design targeted monitoring.

Genomic tailoring of autogenous poultry vaccines to reduce Campylobacter from farm to fork.

Campylobacter is a leading cause of food-borne gastroenteritis worldwide, linked to the consumption of contaminated poultry meat. Targeting this pathogen at source, vaccines for poultry can provide short-term caecal reductions in Campylobacter numbers in the chicken intestine. However, this approach is unlikely to reduce Campylobacter in the food chain or human incidence. This is likely as vaccines typically target only a subset of the high genomic strain diversity circulating among chicken flocks, and rapid evolution diminishes vaccine efficacy over time. To address this, we used a genomic approach to develop a whole-cell autogenous vaccine targeting isolates harbouring genes linked to survival outside of the host. We hyper-immunised a whole major UK breeder farm to passively target offspring colonisation using maternally-derived antibody. Monitoring progeny, broiler flocks revealed a near-complete shift in the post-vaccination Campylobacter population with an ~50% reduction in isolates harbouring extra-intestinal survival genes and a significant reduction of Campylobacter cells surviving on the surface of meat. Based on these findings, we developed a logistic regression model that predicted that vaccine efficacy could be extended to target 65% of a population of clinically relevant strains. Immuno-manipulation of poultry microbiomes towards less harmful commensal isolates by competitive exclusion, has major potential for reducing pathogens in the food production chain.

Human antibodies reveal a protective epitope that is highly conserved among human and nonhuman influenza A viruses.

Influenza remains a serious public health threat throughout the world. Vaccines and antivirals are available that can provide protection from infection. However, new viral strains emerge continuously because of the plasticity of the influenza genome, which necessitates annual reformulation of vaccine antigens, and resistance to antivirals can appear rapidly and become entrenched in circulating virus populations. In addition, the spread of new pandemic strains is difficult to contain because of the time required to engineer and manufacture effective vaccines. Monoclonal antibodies that target highly conserved viral epitopes might offer an alternative protection paradigm. Herein we describe the isolation of a panel of monoclonal antibodies derived from the IgG(+) memory B cells of healthy, human subjects that recognize a previously unknown conformational epitope within the ectodomain of the influenza matrix 2 protein, M2e. This antibody binding region is highly conserved in influenza A viruses, being present in nearly all strains detected to date, including highly pathogenic viruses that infect primarily birds and swine, and the current 2009 swine-origin H1N1 pandemic strain (S-OIV). Furthermore, these human anti-M2e monoclonal antibodies protect mice from lethal challenges with either H5N1 or H1N1 influenza viruses. These results suggest that viral M2e can elicit broadly cross-reactive and protective antibodies in humans. Accordingly, recombinant forms of these human antibodies may provide useful therapeutic agents to protect against infection from a broad spectrum of influenza A strains.

Discovery of novel α7 nicotinic acetylcholine receptor ligands via pharmacophoric and docking studies of benzylidene anabaseine analogs.

Based on pharmacophore elucidation and docking studies on interactions of benzylidene anabaseine analogs with AChBPs and α7 nAChR, novel spirodiazepine and spiroimidazoline quinuclidine series have been designed. Binding studies revealed that some of hydrogen-bond donor containing compounds exhibit improved affinity and selectivity for the α7 nAChR subtype in comparison with most potent metabolite of GTS-21, 3-(4-hydroxy-2-methoxybenzylidene)-anabaseine. Hydrophobicity and rigidity of the ligand also contribute into its binding affinity. We also describe alternative pharmacophoric features equidistant from the carbonyl oxygen atom of the conserved Trp-148 of the principal face, which may be exploited to further design diverse focused libraries targeting the α7 nAChR.

Multiple interaction regions in the orthosteric ligand binding domain of the α7 neuronal nicotinic acetylcholine receptor.

Neuronal nicotinic receptors (nAChRs) belong to the Cys-loop family of ligand-gated ion channels and are formed from five subunits either as homologous or heterologous, oligomeric receptors, and are of interest as targets for treatment of a variety of central and peripheral nervous system disorders. Using a model of the homopentameric α7 nAChR extracellular region derived from the homologous acetylcholine binding protein (AChBP) from Aplysia California, binding modes of structurally diverse, high affinity α7 ligands were examined by docking to the orthosteric ligand binding domain. While all α7 ligands show similar interactions between the essential positively charged cationic center of the ligand and αTRP147 of the receptor (i.e., hydrogen bond to the tryptophan backbone carbonyl and cation-π interaction), docked poses of various ligands show the potential to interact with three additional regions within the binding domain, identified as regions 1, 2, and 3. Region 1 is located in the vicinity of Loop-E, involves ligand-protein interactions via a network of water-mediated hydrogen bonds, and is analogous to the region where pyridinyl groups are located in many of the AChBP-nicotinic ligand cocrystal structures. Ligands interacting with region 2 probe an area that spans from Loop-E to Loops-D and -F and may contribute to α7-selectivity over other nAChR subtypes. Several high affinity α7 ligands show strong interactions in this region. Region 3 is located near Loop-F of the protein and is analogous to an area involved in binding of an active metabolite derived from DMXBA, in an AChBP cocrystal structure. It appears that π-π interactions contribute to binding affinities of α7 nAChR ligands in this latter region, and further, this region may also contribute to α7-selectivity over other nAChR subtypes. Analysis of the resulting poses suggests that compounds with high α7 binding affinity do not require interactions across all regions simultaneously, but that interactions in multiple regions may enhance ligand binding and increase selectivity. Our results provide insight for further development of selective α7 nAChR ligands and may prove useful for the design of novel scaffolds for specific nicotinic therapeutic agents.

Alternative method for assessment of southwestern Atlantic humpback whale population status.

The population of humpback whales (Megaptera novaeangliae) wintering off eastern South America was exploited by commercial whaling almost to the point of extinction in the mid-twentieth century. Since cessation of whaling in the 1970s it is recovering, but the timing and level of recovery is uncertain. We implemented a Bayesian population dynamics model describing the population's trajectory from 1901 and projecting it to 2040 to revise a previous population status assessment that used Sampling-Importance-Resampling in a Bayesian framework. Using our alternative method for model fitting (Markov chain Monte Carlo), which is more widely accessible to ecologists, we replicate a "base case scenario" to verify the effect on model results, and introduce additional data to update the status assessment. Our approach allowed us to widen the previous informative prior on carrying capacity to better reflect scientific uncertainty around historical population levels. The updated model provided more precise estimates for population sizes over the period considered (1901-2040) and suggests that carrying capacity (K: median 22,882, mean 22,948, 95% credible interval [CI] 22,711-23,545) and minimum population size (N1958: median 305, mean 319, 95% CI 271-444) might be lower than previously estimated (K: median 24,558, mean 25,110, 95% CI 22,791-31,118; N1958: median 503, mean 850, 95% CI 159-3,943). However, posterior 95% credible intervals of parameters in the updated model overlap those of the previous study. Our approach provides an accessible framework for investigating the status of depleted animal populations for which information is available on historical mortality (e.g., catches) and intermittent estimates of population size and/or trend.

Integrating disparate datasets to model the functional response of a marine predator: A case study of harbour porpoises in the southern North Sea.

Quantifying consumption and prey choice for marine predator species is key to understanding their interaction with prey species, fisheries, and the ecosystem as a whole. However, parameterizing a functional response for large predators can be challenging because of the difficulty in obtaining the required data on predator diet and on the availability of multiple prey species.This study modeled a multi-species functional response (MSFR) to describe the relationship between consumption by harbour porpoises (Phocoena phocoena) and the availability of multiple prey species in the southern North Sea. Bayesian methodology was employed to estimate MSFR parameters and to incorporate uncertainties in diet and prey availability estimates. Prey consumption was estimated from stomach content data from stranded harbour porpoises. Prey availability to harbour porpoises was estimated based on the spatial overlap between prey distributions, estimated from fish survey data, and porpoise foraging range in the days prior to stranding predicted from telemetry data.Results indicated a preference for sandeels in the study area. Prey switching behavior (change in preference dependent on prey abundance) was confirmed by the favored type III functional response model. Variation in the size of the foraging range (estimated area where harbour porpoises could have foraged prior to stranding) did not alter the overall pattern of the results or conclusions.Integrating datasets on prey consumption from strandings, predator foraging distribution using telemetry, and prey availability from fish surveys into the modeling approach provides a methodological framework that may be appropriate for fitting MSFRs for other predators.

Killer whale (Orcinus orca) population dynamics in response to a period of rapid ecosystem change in the eastern North Atlantic.

This study investigates survival and abundance of killer whales (Orcinus orca) in Norway in 1988-2019 using capture-recapture models of photo-identification data. We merged two datasets collected in a restricted fjord system in 1988-2008 (Period 1) with a third, collected after their preferred herring prey shifted its wintering grounds to more exposed coastal waters in 2012-2019 (Period 2), and investigated any differences between these two periods. The resulting dataset, spanning 32 years, comprised 3284 captures of 1236 whales, including 148 individuals seen in both periods. The best-supported models of survival included the effects of sex and time period, and the presence of transients (whales seen only once). Period 2 had a much larger percentage of transients compared to Period 1 (mean = 30% vs. 5%) and the identification of two groups of whales with different residency patterns revealed heterogeneity in recapture probabilities. This caused estimates of survival rates to be biased downward (females: 0.955 ± 0.027 SE, males: 0.864 ± 0.038 SE) compared to Period 1 (females: 0.998 ± 0.002 SE, males: 0.985 ± 0.009 SE). Accounting for this heterogeneity resulted in estimates of apparent survival close to unity for regularly seen whales in Period 2. A robust design model for Period 2 further supported random temporary emigration at an estimated annual probability of 0.148 (± 0.095 SE). This same model estimated a peak in annual abundance in 2015 at 1061 individuals (95% CI 999-1127), compared to a maximum of 731 (95% CI 505-1059) previously estimated in Period 1, and dropped to 513 (95% CI 488-540) in 2018. Our results indicate variations in the proportion of killer whales present of an undefined population (or populations) in a larger geographical region. Killer whales have adjusted their distribution to shifts in key prey resources, indicating potential to adapt to rapidly changing marine ecosystems.

Ocean warming threatens southern right whale population recovery.

Whales contribute to marine ecosystem functioning, and they may play a role in mitigating climate change and supporting the Antarctic krill (Euphausia superba) population, a keystone prey species that sustains the entire Southern Ocean (SO) ecosystem. By analyzing a five-decade (1971­2017) data series of individual southern right whales (SRWs; Eubalaena australis) photo-identified at Península Valdés, Argentina, we found a marked increase in whale mortality rates following El Niño events. By modeling how the population responds to changes in the frequency and intensity of El Niño events, we found that such events are likely to impede SRW population recovery and could even cause population decline. Such outcomes have the potential to disrupt food-web interactions in the SO, weakening that ecosystem's contribution to the mitigation of climate change at a global scale.

Decline in abundance and apparent survival rates of fin whales (Balaenoptera physalus) in the northern Gulf of St. Lawrence.

Estimates of abundance and survivorship provide quantifiable measures to monitor populations and to define and understand their conservation status. This study investigated changes in abundance and survival rates of fin whales (Balaenoptera physalus) in the northern Gulf of St. Lawrence in the context of anthropogenic pressures and changing environmental conditions. A long-term data set, consisting of 35 years of photo-identification surveys and comprising more than 5,000 identifications of 507 individuals, formed the basis of this mark-recapture study. Based on model selection using corrected Akaike Information Criterion, the most parsimonious Cormack-Jolly-Seber model included a linear temporal trend in noncalf apparent survival rates with a sharp decline in the last 5 years of the study and a median survival rate of 0.946 (95% confidence interval (CI) 0.910-0.967). To account for capture heterogeneity due to divergent patterns of site fidelity, agglomerative hierarchical cluster analysis was employed to categorize individuals based on their annual and survey site fidelity indices. However, the negative trend in survivorship remained and was corroborated by a significant decline in the estimated super-population size from 335 (95% CI 321-348) individuals in 2004-2010 to 291 (95% CI 270-312) individuals in 2010-2016. Concurrently, a negative trend was estimated in recruitment to the population, supported by a sharp decrease in the number of observed calves. Ship strikes and changes in prey availability are potential drivers of the observed decline in fin whale abundance. The combination of clustering methods with mark-recapture represents a flexible way to investigate the effects of site fidelity on demographic variables and is broadly applicable to other individual-based studies.

Variations in age- and sex-specific survival rates help explain population trend in a discrete marine mammal population.

Understanding the drivers underlying fluctuations in the size of animal populations is central to ecology, conservation biology, and wildlife management. Reliable estimates of survival probabilities are key to population viability assessments, and patterns of variation in survival can help inferring the causal factors behind detected changes in population size. We investigated whether variation in age- and sex-specific survival probabilities could help explain the increasing trend in population size detected in a small, discrete population of bottlenose dolphins Tursiops truncatus off the east coast of Scotland. To estimate annual survival probabilities, we applied capture-recapture models to photoidentification data collected from 1989 to 2015. We used robust design models accounting for temporary emigration to estimate juvenile and adult survival, multistate models to estimate sex-specific survival, and age models to estimate calf survival. We found strong support for an increase in juvenile/adult annual survival from 93.1% to 96.0% over the study period, most likely caused by a change in juvenile survival. Examination of sex-specific variation showed weaker support for this trend being a result of increasing female survival, which was overall higher than for males and animals of unknown sex. Calf survival was lower in the first than second year; a bias in estimating third-year survival will likely exist in similar studies. There was some support first-born calf survival being lower than for calves born subsequently. Coastal marine mammal populations are subject to the impacts of environmental change, increasing anthropogenic disturbance and the effects of management measures. Survival estimates are essential to improve our understanding of population dynamics and help predict how future pressures may impact populations, but obtaining robust information on the life history of long-lived species is challenging. Our study illustrates how knowledge of survival can be increased by applying a robust analytical framework to photoidentification data.

A molecular immunology approach to antibody humanization and functional optimization.

We introduce a new method of humanization based on a novel and immunologically relevant metric of antibody humanness, termed human string content (HSC), that quantifies a sequence at the level of potential MHC/T-cell epitopes. Use of this quantity rather than global identity as an optimization goal enables the sampling of human diversity from distinct human germline sequences across the framework and CDR regions, and allows for the generation of multiple diverse candidate sequences. As a result engineering is carried out at finer sequence resolution relative to standard CDR grafting methods, providing for the optimization of antibody properties beyond immunogenicity such as antigen affinity and solution behavior. We have applied this method to the humanization of four antibodies with different antigen specificities. The resulting variable domains differ fundamentally from CDR-grafted antibodies in that they are immunologically more human and their humanness is derived from several discrete germline sequences. Furthermore, these antibodies bind their respective antigens better than or comparable to those of the parent antibodies without the need for affinity maturation.

Role of ECMO in congenital diaphragmatic hernia.

Congenital diaphragmatic hernia (CDH) is typified morphologically by failure of diaphragmatic development with accompanying lung hypoplasia and persistent pulmonary hypertension of the newborn (PPHN). Patients who have labile physiology and low preductal saturations despite optimal ventilatory and inotropic support may be considered for extracorporeal membrane oxygenation (ECMO). Systematic reviews into the benefits of ECMO in CDH concluded that any benefit is unclear. Few randomised trials exist to demonstrate clear benefit and guide management. However, ECMO may have its uses in those that have reversibility of their respiratory disease. A few centres and networks have demonstrated an increase in survival rate by post hoc analysis (based on a difference in referral patterns with the availability of ECMO) in their series. One issue may be that of careful patient selection with regard to reversibility of pathophysiology. At present, there is no single test or prognostication that predicts reversibility of PPHN and criteria for referral for ECMO is undergoing continued refinement. Overall survival is similar between cannulation modes. There is no consensus on the time limit for ECMO runs. The optimal timing of surgery for patients on ECMO is difficult to definitively establish, but it seems that repair at an early stage (with careful perioperative management) is becoming less of a taboo, and may improve outcome and help with either coming off ECMO or decisions on withdrawal later. The provision of ECMO will continue to be evaluated, and prospective randomised trial are needed to help answer question of patient selection and management.

Assessing cetacean surveys throughout the Mediterranean Sea: a gap analysis in environmental space.

Heterogeneous data collection in the marine environment has led to large gaps in our knowledge of marine species distributions. To fill these gaps, models calibrated on existing data may be used to predict species distributions in unsampled areas, given that available data are sufficiently representative. Our objective was to evaluate the feasibility of mapping cetacean densities across the entire Mediterranean Sea using models calibrated on available survey data and various environmental covariates. We aggregated 302,481 km of line transect survey effort conducted in the Mediterranean Sea within the past 20 years by many organisations. Survey coverage was highly heterogeneous geographically and seasonally: large data gaps were present in the eastern and southern Mediterranean and in non-summer months. We mapped the extent of interpolation versus extrapolation and the proportion of data nearby in environmental space when models calibrated on existing survey data were used for prediction across the entire Mediterranean Sea. Using model predictions to map cetacean densities in the eastern and southern Mediterranean, characterised by warmer, less productive waters, and more intense eddy activity, would lead to potentially unreliable extrapolations. We stress the need for systematic surveys of cetaceans in these environmentally unique Mediterranean waters, particularly in non-summer months.

Laparoscopic primary repair of a pediatric transanal impalement injury: a case report.

Conventional treatment of anorectal impalement injuries involves an open exploration and either a fecal diversion and/or a primary repair dictated by the degree of soft-tissue disruption and contamination. In this paper, the authors present the case report of a successful primary laparoscopic repair of an accidental transanal intraperitoneal impalement injury in a child.