Global spatial risk assessment of sharks under the footprint of fisheries.

Effective ocean management and the conservation of highly migratory species depend on resolving the overlap between animal movements and distributions, and fishing effort. However, this information is lacking at a global scale. Here we show, using a big-data approach that combines satellite-tracked movements of pelagic sharks and global fishing fleets, that 24% of the mean monthly space used by sharks falls under the footprint of pelagic longline fisheries. Space-use hotspots of commercially valuable sharks and of internationally protected species had the highest overlap with longlines (up to 76% and 64%, respectively), and were also associated with significant increases in fishing effort. We conclude that pelagic sharks have limited spatial refuge from current levels of fishing effort in marine areas beyond national jurisdictions (the high seas). Our results demonstrate an urgent need for conservation and management measures at high-seas hotspots of shark space use, and highlight the potential of simultaneous satellite surveillance of megafauna and fishers as a tool for near-real-time, dynamic management.

Back to the wild: movements of a juvenile tiger shark released from a public aquarium.

Sharks are an important attraction for aquaria; however, larger species can rarely be kept indefinitely. To date, there has been little work tracking shark movements post-release to the wild. The authors used high-resolution biologgers to monitor a sub-adult tiger shark's pre- and post-release fine-scale movements following 2 years of captivity in an aquarium. They also compared its movement with that of a wild shark tagged nearby. Despite the differences in movement between the two sharks, with vertical oscillations notably absent and greater levels of turning seen from the released shark, the captive shark survived the release. These biologgers improve insight into post-release movements of captive sharks.

Maximum Relevance Minimum Redundancy Dropout with Informative Kernel Determinantal Point Process.

In recent years, deep neural networks have shown significant progress in computer vision due to their large generalization capacity; however, the overfitting problem ubiquitously threatens the learning process of these highly nonlinear architectures. Dropout is a recent solution to mitigate overfitting that has witnessed significant success in various classification applications. Recently, many efforts have been made to improve the Standard dropout using an unsupervised merit-based semantic selection of neurons in the latent space. However, these studies do not consider the task-relevant information quality and quantity and the diversity of the latent kernels. To solve the challenge of dropping less informative neurons in deep learning, we propose an efficient end-to-end dropout algorithm that selects the most informative neurons with the highest correlation with the target output considering the sparsity in its selection procedure. First, to promote activation diversity, we devise an approach to select the most diverse set of neurons by making use of determinantal point process (DPP) sampling. Furthermore, to incorporate task specificity into deep latent features, a mutual information (MI)-based merit function is developed. Leveraging the proposed MI with DPP sampling, we introduce the novel DPPMI dropout that adaptively adjusts the retention rate of neurons based on their contribution to the neural network task. Empirical studies on real-world classification benchmarks including, MNIST, SVHN, CIFAR10, CIFAR100, demonstrate the superiority of our proposed method over recent state-of-the-art dropout algorithms in the literature.

A Comparison Among the Prevalence of Alexithymia in Patients With Psychogenic Nonepileptic Seizures, Epilepsy, and the Healthy Population: A Systematic Review of the Literature.

BACKGROUND: The construct of alexithymia includes a deficit in identifying and describing feelings. It has been proposed that alexithymia plays a role in the etiology of PNES but patients with epilepsy have also scored high on measures of alexithymia. OBJECTIVES: To determine the prevalence of alexithymia in patients with psychogenic nonepileptic seizures (PNES) and to compare it with patients with epilepsy and healthy controls. METHODS: We performed a systematic review of the literature based on Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines. We searched MEDLINE, EMBASE, and PsycINFO databases. Studies using the Toronto Alexithymia Scale (TAS-20) to measure alexithymia in adult patients with PNES, were compared with a control group (epilepsy or healthy controls). RESULTS: Six studies were included in this review. A total of 364 patients with PNES, 234 patients with epilepsy, and 129 healthy controls participated in these studies. Prevalence of alexithymia in PNES (30-90%) was higher than those in the healthy population (5-14%), but not significantly different from those with epilepsy (26-76%). In 3 studies the results were controlled for depression and anxiety. One study found a small correlation between alexithymia and a history of abuse (r = 0.15). Alexithymia appears to mediate perceived quality of life. CONCLUSIONS: This review suggests that the prevalence of alexithymia in patients with PNES is similar to that in patients with epilepsy, both significantly higher than those in the healthy population. This finding can point to shared psychiatric and psychosocial factors between these patients. Therapies aimed at increasing emotional awareness may be important in improving quality of life.

Prenatal thrombosis of the ductus arteriosus.

Spontaneous thrombus in the ductus arteriosus, without associated ductal aneurysm, is a rare condition. We report successful management with clinical and echocardiographic follow-up in a newborn with prenatal diagnosis.

High-throughput expression of animal venom toxins in Escherichia coli to generate a large library of oxidized disulphide-reticulated peptides for drug discovery.

BACKGROUND: Animal venoms are complex molecular cocktails containing a wide range of biologically active disulphide-reticulated peptides that target, with high selectivity and efficacy, a variety of membrane receptors. Disulphide-reticulated peptides have evolved to display improved specificity, low immunogenicity and to show much higher resistance to degradation than linear peptides. These properties make venom peptides attractive candidates for drug development. However, recombinant expression of reticulated peptides containing disulphide bonds is challenging, especially when associated with the production of large libraries of bioactive molecules for drug screening. To date, as an alternative to artificial synthetic chemical libraries, no comprehensive recombinant libraries of natural venom peptides are accessible for high-throughput screening to identify novel therapeutics. RESULTS: In the accompanying paper an efficient system for the expression and purification of oxidized disulphide-reticulated venom peptides in Escherichia coli is described. Here we report the development of a high-throughput automated platform, that could be adapted to the production of other families, to generate the largest ever library of recombinant venom peptides. The peptides were produced in the periplasm of E. coli using redox-active DsbC as a fusion tag, thus allowing the efficient formation of correctly folded disulphide bridges. TEV protease was used to remove fusion tags and recover the animal venom peptides in the native state. Globally, within nine months, out of a total of 4992 synthetic genes encoding a representative diversity of venom peptides, a library containing 2736 recombinant disulphide-reticulated peptides was generated. The data revealed that the animal venom peptides produced in the bacterial host were natively folded and, thus, are putatively biologically active. CONCLUSIONS: Overall this study reveals that high-throughput expression of animal venom peptides in E. coli can generate large libraries of recombinant disulphide-reticulated peptides of remarkable interest for drug discovery programs.

Gene design, fusion technology and TEV cleavage conditions influence the purification of oxidized disulphide-rich venom peptides in Escherichia coli.

BACKGROUND: Animal venoms are large, complex libraries of bioactive, disulphide-rich peptides. These peptides, and their novel biological activities, are of increasing pharmacological and therapeutic importance. However, recombinant expression of venom peptides in Escherichia coli remains difficult due to the significant number of cysteine residues requiring effective post-translational processing. There is also an urgent need to develop high-throughput recombinant protocols applicable to the production of reticulated peptides to enable efficient screening of their drug potential. Here, a comprehensive study was developed to investigate how synthetic gene design, choice of fusion tag, compartment of expression, tag removal conditions and protease recognition site affect levels of solubility of oxidized venom peptides produced in E. coli. RESULTS: The data revealed that expression of venom peptides imposes significant pressure on cysteine codon selection. DsbC was the best fusion tag for venom peptide expression, in particular when the fusion was directed to the bacterial periplasm. While the redox activity of DsbC was not essential to maximize expression of recombinant fusion proteins, redox activity did lead to higher levels of correctly folded target peptides. With the exception of proline, the canonical TEV protease recognition site tolerated all other residues at its C-terminus, confirming that no non-native residues, which might affect activity, need to be incorporated at the N-terminus of recombinant peptides for tag removal. CONCLUSIONS: This study reveals that E. coli is a convenient heterologous host for the expression of soluble and functional venom peptides. Using the optimal construct design, a large and diverse range of animal venom peptides were produced in the µM scale. These results open up new possibilities for the high-throughput production of recombinant disulphide-rich peptides in E. coli.

Predicting occurrence of juvenile shark habitat to improve conservation planning.

Fishing and habitat degradation have increased the extinction risk of sharks, and conservation strategies recognize that survival of juveniles is critical for the effective management of shark populations. Despite the rapid expansion of marine protected areas (MPAs) globally, the paucity of shark-monitoring data on large scales (100s-1000s km) means that the effectiveness of MPAs in halting shark declines remains unclear. Using data collected by baited remote underwater video systems (BRUVS) in northwestern Australia, we developed generalized linear models to elucidate the ecological drivers of habitat suitability for juvenile sharks. We assessed occurrence patterns at the order and species levels. We included all juvenile sharks sampled and the 3 most abundant species sampled separately (grey reef [Carcharhinus amblyrhynchos], sandbar [Carcharhinus plumbeus], and whitetip reef sharks [Triaenodon obesus]). We predicted the occurrence of juvenile sharks across 490,515 km2 of coastal waters and quantified the representation of highly suitable habitats within MPAs. Our species-level models had higher accuracy (ĸ ≥ 0.69) and deviance explained (≥48%) than our order-level model (ĸ = 0.36 and deviance explained of 10%). Maps of predicted occurrence revealed different species-specific patterns of highly suitable habitat. These differences likely reflect different physiological or resource requirements between individual species and validate concerns over the utility of conservation targets based on aggregate species groups as opposed to a species-focused approach. Highly suitable habitats were poorly represented in MPAs with the most restrictions on extractive activities. This spatial mismatch possibly indicates a lack of explicit conservation targets and information on species distribution during the planning process. Non-extractive BRUVS provided a useful platform for building the suitability models across large scales to assist conservation planning across multiple maritime jurisdictions, and our approach provides a simple for method for testing the effectiveness of MPAs.

Development of a gene synthesis platform for the efficient large scale production of small genes encoding animal toxins.

BACKGROUND: Gene synthesis is becoming an important tool in many fields of recombinant DNA technology, including recombinant protein production. De novo gene synthesis is quickly replacing the classical cloning and mutagenesis procedures and allows generating nucleic acids for which no template is available. In addition, when coupled with efficient gene design algorithms that optimize codon usage, it leads to high levels of recombinant protein expression. RESULTS: Here, we describe the development of an optimized gene synthesis platform that was applied to the large scale production of small genes encoding venom peptides. This improved gene synthesis method uses a PCR-based protocol to assemble synthetic DNA from pools of overlapping oligonucleotides and was developed to synthesise multiples genes simultaneously. This technology incorporates an accurate, automated and cost effective ligation independent cloning step to directly integrate the synthetic genes into an effective Escherichia coli expression vector. The robustness of this technology to generate large libraries of dozens to thousands of synthetic nucleic acids was demonstrated through the parallel and simultaneous synthesis of 96 genes encoding animal toxins. CONCLUSIONS: An automated platform was developed for the large-scale synthesis of small genes encoding eukaryotic toxins. Large scale recombinant expression of synthetic genes encoding eukaryotic toxins will allow exploring the extraordinary potency and pharmacological diversity of animal venoms, an increasingly valuable but unexplored source of lead molecules for drug discovery.

Genetic and functional analyses of SHANK2 mutations suggest a multiple hit model of autism spectrum disorders.

Autism spectrum disorders (ASD) are a heterogeneous group of neurodevelopmental disorders with a complex inheritance pattern. While many rare variants in synaptic proteins have been identified in patients with ASD, little is known about their effects at the synapse and their interactions with other genetic variations. Here, following the discovery of two de novo SHANK2 deletions by the Autism Genome Project, we identified a novel 421 kb de novo SHANK2 deletion in a patient with autism. We then sequenced SHANK2 in 455 patients with ASD and 431 controls and integrated these results with those reported by Berkel et al. 2010 (n = 396 patients and n = 659 controls). We observed a significant enrichment of variants affecting conserved amino acids in 29 of 851 (3.4%) patients and in 16 of 1,090 (1.5%) controls (P = 0.004, OR = 2.37, 95% CI = 1.23-4.70). In neuronal cell cultures, the variants identified in patients were associated with a reduced synaptic density at dendrites compared to the variants only detected in controls (P = 0.0013). Interestingly, the three patients with de novo SHANK2 deletions also carried inherited CNVs at 15q11-q13 previously associated with neuropsychiatric disorders. In two cases, the nicotinic receptor CHRNA7 was duplicated and in one case the synaptic translation repressor CYFIP1 was deleted. These results strengthen the role of synaptic gene dysfunction in ASD but also highlight the presence of putative modifier genes, which is in keeping with the "multiple hit model" for ASD. A better knowledge of these genetic interactions will be necessary to understand the complex inheritance pattern of ASD.

Fingerprint Liveness Detection in the Presence of Capable Intruders.

Fingerprint liveness detection methods have been developed as an attempt to overcome the vulnerability of fingerprint biometric systems to spoofing attacks. Traditional approaches have been quite optimistic about the behavior of the intruder assuming the use of a previously known material. This assumption has led to the use of supervised techniques to estimate the performance of the methods, using both live and spoof samples to train the predictive models and evaluate each type of fake samples individually. Additionally, the background was often included in the sample representation, completely distorting the decision process. Therefore, we propose that an automatic segmentation step should be performed to isolate the fingerprint from the background and truly decide on the liveness of the fingerprint and not on the characteristics of the background. Also, we argue that one cannot aim to model the fake samples completely since the material used by the intruder is unknown beforehand. We approach the design by modeling the distribution of the live samples and predicting as fake the samples very unlikely according to that model. Our experiments compare the performance of the supervised approaches with the semi-supervised ones that rely solely on the live samples. The results obtained differ from the ones obtained by the more standard approaches which reinforces our conviction that the results in the literature are misleadingly estimating the true vulnerability of the biometric system.

Predicting current and future global distributions of whale sharks.

The Vulnerable (IUCN) whale shark spans warm and temperate waters around the globe. However, their present-day and possible future global distribution has never been predicted. Using 30 years (1980-2010) of whale shark observations recorded by tuna purse-seiners fishing in the Atlantic, Indian and Pacific Oceans, we applied generalized linear mixed-effects models to test the hypothesis that similar environmental covariates predict whale shark occurrence in all major ocean basins. We derived global predictors from satellite images for chlorophyll a and sea surface temperature, and bathymetric charts for depth, bottom slope and distance to shore. We randomly generated pseudo-absences within the area covered by the fisheries, and included fishing effort as an offset to account for potential sampling bias. We predicted sea surface temperatures for 2070 using an ensemble of five global circulation models under a no climate-policy reference scenario, and used these to predict changes in distribution. The full model (excluding standard deviation of sea surface temperature) had the highest relative statistical support (wAICc  = 0.99) and explained ca. 60% of the deviance. Habitat suitability was mainly driven by spatial variation in bathymetry and sea surface temperature among oceans, although these effects differed slightly among oceans. Predicted changes in sea surface temperature resulted in a slight shift of suitable habitat towards the poles in both the Atlantic and Indian Oceans (ca. 5°N and 3-8°S, respectively) accompanied by an overall range contraction (2.5-7.4% and 1.1-6.3%, respectively). Predicted changes in the Pacific Ocean were small. Assuming that whale shark environmental requirements and human disturbances (i.e. no stabilization of greenhouse gas emissions) remain similar, we show that warming sea surface temperatures might promote a net retreat from current aggregation areas and an overall redistribution of the species.

Links between the three-dimensional movements of whale sharks (Rhincodon typus) and the bio-physical environment off a coral reef.

BACKGROUND: Measuring coastal-pelagic prey fields at scales relevant to the movements of marine predators is challenging due to the dynamic and ephemeral nature of these environments. Whale sharks (Rhincodon typus) are thought to aggregate in nearshore tropical waters due to seasonally enhanced foraging opportunities. This implies that the three-dimensional movements of these animals may be associated with bio-physical properties that enhance prey availability. To date, few studies have tested this hypothesis. METHODS: Here, we conducted ship-based acoustic surveys, net tows and water column profiling (salinity, temperature, chlorophyll fluorescence) to determine the volumetric density, distribution and community composition of mesozooplankton (predominantly euphausiids and copepods) and oceanographic properties of the water column in the vicinity of whale sharks that were tracked simultaneously using satellite-linked tags at Ningaloo Reef, Western Australia. Generalised linear mixed effect models were used to explore relationships between the 3-dimensional movement behaviours of tracked sharks and surrounding prey fields at a spatial scale of ~ 1 km. RESULTS: We identified prey density as a significant driver of horizontal space use, with sharks occupying areas along the reef edge where densities were highest. These areas were characterised by complex bathymetry such as reef gutters and pinnacles. Temperature and salinity profiles revealed a well-mixed water column above the height of the bathymetry (top 40 m of the water column). Regions of stronger stratification were associated with reef gutters and pinnacles that concentrated prey near the seabed, and entrained productivity at local scales (~ 1 km). We found no quantitative relationship between the depth use of sharks and vertical distributions of horizontally averaged prey density. Whale sharks repeatedly dove to depths where spatially averaged prey concentration was highest but did not extend the time spent at these depth layers. CONCLUSIONS: Our work reveals previously unrecognized complexity in interactions between whale sharks and their zooplankton prey.

Deep Learning-Based Classification of Early-Stage Mycosis Fungoides and Benign Inflammatory Dermatoses on H&E-Stained Whole-Slide Images: A Retrospective, Proof-of-Concept Study.

The diagnosis of early-stage mycosis fungoides (MF) is challenging owing to shared clinical and histopathological features with benign inflammatory dermatoses. Recent evidence has shown that deep learning (DL) can assist pathologists in cancer classification, but this field is largely unexplored for cutaneous lymphomas. This study evaluates DL in distinguishing early-stage MF from benign inflammatory dermatoses using a unique dataset of 924 H&E-stained whole-slide images from skin biopsies, including 233 patients with early-stage MF and 353 patients with benign inflammatory dermatoses. All patients with MF were diagnosed after clinicopathological correlation. The classification accuracy of weakly supervised DL models was benchmarked against 3 expert pathologists. The highest performance on a temporal test set was at ×200 magnification (0.50 µm per pixel resolution), with a mean area under the curve of 0.827 ± 0.044 and a mean balanced accuracy of 76.2 ± 3.9%. This nearly matched the 77.7% mean balanced accuracy of the 3 expert pathologists. Most (63.5%) attention heatmaps corresponded well with the pathologists' region of interest. Considering the difficulty of the MF versus benign inflammatory dermatoses classification task, the results of this study show promise for future applications of weakly supervised DL in diagnosing early-stage MF. Achieving clinical-grade performance will require larger multi-institutional datasets and improved methodologies, such as multimodal DL with incorporation of clinical data.

Designing a Nurse-Led Program for Self-Management of Substance Addiction Consequences: A Modified e-Delphi Study.

Therapeutic interventions for people with problematic use of psychoactive substances can help tackle specific needs related to substance addiction consequences. This modified e-Delphi study aimed to establish consensus on a training program for self-management of substance addiction consequences. The study was conducted between February and April 2022, with an experts' sample of 28 participants in the first round and 24 in the second. A priori consensus criteria were defined for each round. The results revealed a very strong consensus was achieved on the structure of the program and on clinical areas, such as the problematic use of substances, general health knowledge, health-seeking behavior and adherence, self-knowledge and well-being, social role and personal dignity, and family process. Additionally, over 80% participant consensus was achieved on an extensive number of interventions categorized as psychoeducational, psychotherapeutic, socio therapeutic, brief interventions, social skills training, problem solving techniques, relaxation techniques, and counseling. These findings may be able to fulfill a gap concerning structured treatment approaches for people with problematic use of psychoactive substances. Supporting self-management of the consequences of substance addiction and its application can change nurses' interventions.

Acceptability and applicability of an intervention programme with substance addicts. / Aceitabilidade e aplicabilidade de um programa de intervenção com usuários dependentes de substâncias.

The complexity of the problems related to the harmful use of substances requires regular questioning of practices. This article aims to explore the acceptability and applicability of an intervention programme for patients with problematic substance use. Qualitative study. Data collection, through a focus group with 6 nurses and 6 semi-structured interviews with patients under treatment. We have used lexicographic textual analysis. From the focus group, 151 text segments were analysed, retaining 85.8% of the total for the creation of five classes. An analysis of similarity led to the formation of two central nuclei, represented by the words "Nursing" and "Intervention". From interviews, 252 text segments were analysed, retaining 71.83% for the creation of 5 classes. An analysis of similarity led to the formation of three central nuclei, represented by the words "want", "programme" and "see". Nurses recognise the need for a more structured and flexible approach focused on people's needs. Users also affirm the need for flexible interventions, without a pre-established time frame, that promote labour integration, therapeutic support for abstinence and management of comorbidities.

A complexidade dos problemas relacionados com o uso problemático de substâncias requer questionamento regular das práticas. O objetivo deste artigo é explorar a aceitabilidade e a aplicabilidade de um programa de intervenção com pessoas dependentes de substâncias. Estudo qualitativo. Recolha de dados, realizada através de 1 grupo focal com 6 enfermeiros e 6 entrevistas semiestruturadas a usuários em tratamento. Utilizou-se à análise textual lexicográfica. No grupo focal, foram analisados 151 segmentos de texto, retendo 85,8% do total para a criação de cinco classes. A análise de similitude conduziu à formação de dois núcleos centrais, representados pelas palavras: Enfermeiro e Intervenção. Das entrevistas, foram analisados 252 segmentos de texto, retendo 71,83% para a criação de 5 classes. A análise de similitude conduziu à formação de três núcleos centrais, representados pelas palavras: querer, programa e ver. Os enfermeiros reconhecem a necessidade de uma abordagem mais estruturada, centrada nas necessidades das pessoas e flexível. Os usuários, acrescentam a necessidade de ser flexível, sem tempo definido à partida, promovendo trabalho, suporte terapêutico para abstinência e gestão das comorbilidades.