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The project "Northwest Rock Art Route" aims to explore Portuguese NW rock art resource potentialities as capable of increase sustainable development of touristic practices. The Portuguese NW is rich in open-air post-Palaeolithic rock art, especially from the designated Atlantic Art, specific from the area. Along with its scientific value, its strategic character should integrate programs of territory development and organization. In order to achieve that, some scientific needs have to be overcome, like data compilation and systematization, promoting scientific knowledge and allowing attractive discourses to general public. In order to achieve that, some scientific needs have to be overcome, like data compilation and systematization, promoting scientific knowledge and allowing attractive discourses to general public. The materialized and/or in process of materialization actions will be presented, so as the different achieved results from each NW area. [ABSTRACT FROM AUTHOR]

The present study examined the natural history of fracture and vitamin D levels in Duchenne muscular dystrophy patients, who are vulnerable to osteoporosis and fractures. Retrospective analysis of a cohort of 48 Duchenne muscular dystrophy patients revealed that 43% of patients experienced ≥1 fracture. Fracture probabilities at ages 6, 9, 12, and 15 years were 4%, 9%, 31%, and 60% respectively, accelerating around the time of ambulation loss (mean age 11.8 ± 2.7 years). Chronic corticosteroid therapy was utilized in 69% of patients and was associated with all vertebral fractures. A history of vitamin D deficiency occurred in 84%, and 35% were currently deficient. Despite chronic vitamin D supplementation, 38% remained deficient. These results demonstrate that osteoporosis and fracture remain major concerns in Duchenne muscular dystrophy. Bone health should be optimized well before loss of ambulation, however current levels of vitamin D supplementation may be inadequate given high levels of deficiency. [ABSTRACT FROM AUTHOR]

In 2021, our research group published the prominent anticancer activity achieved through the successful combination of two redox centres (ortho-quinone/para-quinone or quinone/selenium-containing triazole) through a copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction. The combination of two naphthoquinoidal substrates towards a synergetic product was indicated, but not fully explored. Herein, we report the synthesis of 15 new quinone-based derivatives prepared from click chemistry reactions and their subsequent evaluation against nine cancer cell lines and the murine fibroblast line L929. Our strategy was based on the modification of the A-ring of para-naphthoquinones and subsequent conjugation with different ortho-quinoidal moieties. As anticipated, our study identified several compounds with IC50 values below 0.5 µM in tumour cell lines. Some of the compounds described here also exhibited an excellent selectivity index and low cytotoxicity on L929, the control cell line. The antitumour evaluation of the compounds separately and in their conjugated form proved that the activity is strongly enhanced in the derivatives containing two redox centres. Thus, our study confirms the efficiency of using A-ring functionalized para-quinones coupled with ortho-quinones to obtain a diverse range of two redox centre compounds with potential applications against cancer cell lines. Here as well, it literally takes two for an efficient tango! [ABSTRACT FROM AUTHOR]

We introduce an Autonomic System to perform management of energy consumption in Internet of Things (IoT) devices and Fog Computing, including an advanced orchestration mechanisms to manage dynamic duty cycles for extra energy savings. The solution works by adjusting Home (H) and Away (A) cycles based on contextual information, like environmental conditions, user behavior, behavior variation, regulations on energy and network resources utilization, among others. Performance analysis through a proof-of-concept implementation presents average energy savings of up to 61.51% when augmenting with a scheduling system and variable long sleep cycles (LS), and potential for 75.9% savings in specific conditions. We also concluded that there is no linear relation between increasing LS time and additional savings. The significance of this research is to promote autonomic management as a solution to develop more energy efficient buildings and smarter cities, towards sustainable goals. [Display omitted] • Internet of Things energy management in large scale environment with Fog Computing. • Fog (and Mist) network performance analysis with queueing theory. • Network delay and device's duty-cycle real-time system's limitations. • Network energy savings with Autonomic device's dynamic duty-cycle operations. [ABSTRACT FROM AUTHOR]

Background: Variants in dehydrodolichol diphosphate synthetase (DHDDS) and nuclear undecaprenyl pyrophosphate synthase 1 (NUS1) cause a neurodevelopmental disorder, classically with prominent epilepsy. Recent reports suggest a complex movement disorder and an overlapping phenotype has been postulated due to their combined role in dolichol synthesis. Cases: We describe three patients with heterozygous variants in DHDDS and five with variants affecting NUS1. They bear a remarkably similar phenotype of a movement disorder dominated by multifocal myoclonus. Diagnostic clues include myoclonus exacerbated by action and facial involvement, and slowly progressive or stable, gait ataxia with disproportionately impaired tandem gait. Myoclonus is confirmed with neurophysiology, including EMG of facial muscles. Literature Review: Ninety‐eight reports of heterozygous variants in DHDDS, NUS1 and chromosome 6q22.1 structural alterations spanning NUS1, confirm the convergent phenotype of hypotonia at birth, developmental delay, multifocal myoclonus, ataxia, dystonia and later parkinsonism with or without generalized epilepsy. Other features include periodic exacerbations, stereotypies, anxiety, and dysmorphisms. Although their gene products contribute to dolichol biosynthesis, a key step in N‐glycosylation, transferrin isoform profiles are typically normal. Imaging is normal or non‐specific. Conclusions: Recognition of their shared phenotype may expedite diagnosis through chromosomal microarray and by including DHDDS/NUS1 in movement disorder gene panels. [ABSTRACT FROM AUTHOR]

Children with neuromuscular disorders (NMDs) may experience a spectrum of nutritional issues with adverse health consequences. This review summarizes the current understanding of nutritional care in pediatric NMDs, recognizing disease-specific aspects of nutrition alongside the challenges and needs in dietetic care. General or disease-related nutritional issues for children with NMDs include being underweight, overweight, or obese and having swallowing difficulty, gastroesophageal reflux, diarrhea, and/or constipation. Specific challenges in NMD nutritional assessment include alterations in body composition and energy requirements and difficulties in measuring anthropometry. Multidisciplinary dietetic intervention focuses on optimizing nutrient intakes to avert growth failure or obesity and managing feeding difficulties and gastrointestinal problems. Care guidelines are disease specific and vary in approach and detail. To promote best clinical practice across diverse settings, a standardized approach to assessing growth and nutrition across all pediatric NMDs is needed to direct optimal care centered on individual requirements. Future studies should focus on determining the prevalence of specific nutritional issues and the effectiveness of specific interventions among various pediatric NMD populations. [ABSTRACT FROM AUTHOR]

Paediatric motor neuron diseases encompass a group of neurodegenerative diseases characterised by the onset of muscle weakness and atrophy before the age of 18 years, attributable to motor neuron loss across various neuronal networks in the brain and spinal cord. While the genetic underpinnings are diverse, advances in next generation sequencing have transformed diagnostic paradigms. This has reinforced the clinical phenotyping and molecular genetic expertise required to navigate the complexities of such diagnoses. In turn, improved genetic technology and subsequent gene identification have enabled further insights into the mechanisms of motor neuron degeneration and how these diseases form part of a neurodegenerative disorder spectrum. Common pathophysiologies include abnormalities in axonal architecture and function, RNA processing, and protein quality control. This review incorporates an overview of the clinical manifestations, genetics, and pathophysiology of inherited paediatric motor neuron disorders beyond classic SMN1-related spinal muscular atrophy and describes recent advances in next generation sequencing and its clinical application. Specific disease-modifying treatment is becoming a clinical reality in some disorders of the motor neuron highlighting the importance of a timely and specific diagnosis. [ABSTRACT FROM AUTHOR]

Aim: To improve delivery of acute therapies for acute ischaemic stroke (AIS). Method: We identified factors influencing the speed of diagnosis and delivery of acute therapies in a prospective cohort of 21 children with suspected AIS (eight with AIS, 13 stroke mimics) and explored them in a retrospective cohort with confirmed AIS. Results: Approximately half of the prospective and total AIS cohorts presented with acute, sustained hemiparesis, and were diagnosed relatively quickly. AIS was suspected and diagnosed more slowly in the half presenting with symptoms other than sustained hemiparesis. Thirty‐one out of 51 patients with AIS (19 females, 32 males, mean age 8 years 6 months, SD 5 years 4 months) had arterial abnormalities identified by computed tomography angiography (CTA) or magnetic resonance angiography (MRA): 11 with large vessel occlusion, six with dissection, five with moyamoya disease, nine with other arteriopathies. Among these patients, those initially imaged with CTA were diagnosed more quickly than those with initial magnetic resonance imaging/angiography, which facilitated thrombectomy and thrombolytic therapy. Twenty out of 51 had AIS without arterial abnormalities on CTA or MRA: eight with lenticulostriate vasculopathy and 12 with other small‐vessel AIS. Among these patients, 80% were ineligible for thrombolysis for reasons beyond delay to diagnosis, and all showed good outcomes with supportive treatments alone. Interpretation: Clinical features at presentation influence rapidity with which childhood AIS is suspected and diagnosed. Readily available CTA can direct thrombectomy in patients with large vessel occlusion and thrombolysis in most, but not all, eligible patients. What this paper adds: Children with acute ischaemic stroke (AIS) commonly present with symptoms other than sustained hemiparesis.Stroke is more slowly recognized in these patients, which limits potential therapies.Computed tomography angiography (CTA) accurately identifies AIS with large vessel occlusion, enabling timely endovascular thrombectomy.CTA is sufficient to direct thrombolytic therapy in most eligible children.Most childhood AIS without arterial abnormalities identified by CTA had good outcomes. [ABSTRACT FROM AUTHOR]

Aim: This study dynamically designed, evaluated, and implemented the components of an Australian newborn bloodspot screening (NBS) pilot programme for spinal muscular atrophy (SMA). Method: We used an implementation‐effectiveness study design and continuous interdisciplinary review to measure SMA NBS test protocol performance, identify and overcome laboratory and clinical barriers to implementation, and describe progress during the 2‐year pilot study. Results: The NBS programme screened 252 081 newborn infants from 1st August 2018 to 31st January 2021. Using an NBS pilot test protocol, 21 infants were diagnostically confirmed with SMA. The NBS pilot test protocol had a sensitivity of 100%, specificity greater than 99.9%, false‐positive rate less than 0.001%, a false‐negative rate of 0%, and positive predictive value of 95.5%. A severe phenotype was predicted on the basis of two copies of SMN2 in 57.2% of newborn infants screening positive for SMA. Clinical signs consistent with SMA were evident in 6 out of 21 screen‐positive newborn infants within the first 4 weeks of life. A multidisciplinary team establishing strong partnerships across clinical and laboratory staff was key to implementation. Interpretation: This pilot programme suggests that NBS is essential for early identification of newborn infants at risk of SMA and can be effectively translated into clinical practice. This original article is commented by Mueller‐Felber on page 535 of this issue. [ABSTRACT FROM AUTHOR]

Objective: To provide a greater understanding of the tolerability, safety and clinical outcomes of onasemnogene abeparvovec in real‐world practice, in a broad population of infants with spinal muscular atrophy (SMA). Methods: A prospective cohort study of children with SMA treated with onasemnogene abeparvovec at Sydney Children's Hospital Network, Australia was conducted from August 2019 to November 2021. Safety outcomes included clinical and laboratory evaluations. Efficacy assessments included World Health Organisation (WHO) motor milestones, oral and swallowing abilities, and requirements for respiratory support. The implementation of a model of care for onasemnogene abeparvovec administration in health practice is described. Results: 21 children were treated (age range, 0.65–24 months; body weight range, 2.5–12.5 kg) and 19/21 (90.4%) had previous nusinersen. Transient treatment‐related side effects occurred in all children; vomiting (100%), transaminitis (57%) and thrombocytopaenia (33%). Incidence of moderate/severe transaminitis was significantly greater in infants weighing ≥8 kg compared with <8 kg (p < 0.05). Duration of prednisolone following treatment was prolonged (mean 87.5 days, range 57–274 days). 16/21 (76%) children gained at least one WHO motor milestone. Stabilisation or improvement in bulbar or respiratory function was observed in 20/21 (95.2%) patients. Implementation challenges were mitigated by developing standard operating procedures and facilitating exchange of knowledge. Interpretation: This study provides real‐world evidence to inform treatment decisions and guide therapeutic expectations for onasemnogene abeparvovec and combination therapy for SMA in health practice, especially for children weighing ≥8 kg receiving higher vector loads. Proactive clinical and laboratory surveillance is essential to facilitate individualised management of risks. [ABSTRACT FROM AUTHOR]

• DMD point variants should be carefully analysed in boys with a high CK. • Pre-mRNA splicing studies may clarify pathogenicity of point variants in DMD. • Muscle biopsy remains a useful diagnostic tool in selected cases of dystrophinopathy. A precise genetic diagnosis of a dystrophinopathy has far-reaching implications for affected boys and their families. We present three boys with DMD single nucleotide variants associated with Becker muscular dystrophy presenting with myalgia, reduced exercise capacity, neurodevelopmental symptoms and elevated creatine kinase. The DMD variants were difficult to classify: AIII:1 a synonymous variant in exon 13 c.1602G>A, p.Lys534Lys; BIII:1 an essential splice-site variant in intron 33 c.4674+1G>A, and CII:1 a missense mutation within the cysteine-rich domain, exon 66 c.9619T>C, p.Cys3207Arg. Complementary DNA (cDNA) analysis using muscle-derived mRNA established splice-altering effects of variants for AIII:1 and BIII:1, and normal splicing in CII:1. Western blot analysis demonstrated mildly to moderately reduced dystrophin levels (17.6 – 36.1% the levels of controls), supporting dystrophinopathy as a probable diagnosis. These three cases highlight the diagnostic utility of muscle biopsy for mRNA studies and western blot to investigate DMD variants of uncertain pathogenicity, by exploring effects on splicing and dystrophin protein levels. [ABSTRACT FROM AUTHOR]

Introduction: Biomarkers of disease severity in Charcot-Marie-Tooth disease (CMT) are required to evaluate early responses to treatment. In this study we used magnetic resonance imaging (MRI) to evaluate the relationship between muscle volume and intramuscular fat accumulation with weakness, disability, and impaired gait in affected children and adolescents.Methods: Fifty-five participants underwent MRI of the anterior compartment of the lower leg. Muscle and fat volumes were calculated. Strength was measured using hand-held dynamometry, disability using the CMT Pediatric Scale, and 3-dimensional gait analysis using an 8-camera Vicon Nexus motion capture system.Results: Lower muscle volume was significantly associated with reduced dorsiflexion strength, increased disability, impaired gait profile score, and foot drop. Intramuscular fat accumulation was associated with reduced dorsiflexion strength and impaired gait profile score.Discussion: The MRI protocol described was feasible, reliable, and sensitive to the magnitude of weakness, disability, and walking difficulties in children with CMT. Muscle Nerve 59:213-217, 2019. [ABSTRACT FROM AUTHOR]

Many genetic subtypes of Charcot-Marie-Tooth disease (CMT) show signs of symptomatic disease during the earliest years of life. This might be the ideal time to intervene before progression of clinical sequelae due to demyelination and axonal loss. In the absence of disease-specific clinical trial outcome measures for CMT during infancy and early childhood the aim of this study was to develop and validate a functional measure of disease severity, known as the Charcot-Marie-Tooth disease Infant Scale (CMTInfS). Development projects involved identification of a preliminary pool of 31 items representing the range of disability in affected patients aged 0-4 years from a systematic review of the literature, peer review by 12 expert clinicians and researchers in the field, design of a scoring algorithm and pilot testing in 22 participants. Subsequently, a series of validation projects were conducted based on 128 assessments of: 26 confirmed cases of inherited neuropathy (17 CMT1A, one CMT1B, one CMT1D, one CMT2C, one CMT2S, two CMT4C, one CMTX3, one Riboflavin Transporter Deficiency Type 2, and one unidentified mutation); seven 'at risk' cases and 95 unaffected healthy controls recruited through the NIH-funded Inherited Neuropathies Consortium. Validation projects included: Item, Factor and Rasch analysis, intra- and inter-rater reliability, discriminant ability and convergent validity with the CMT Pediatric Scale (CMTPedS) for children aged 3-4 years. Development and validation projects produced a psychometrically robust 15-item scale. Rasch analysis supported the viability of the CMTInfS as a unidimensional measure of disease severity and showed good overall model fit, no evidence of misfitting items or persons and was well targeted for affected children. The CMTInfS demonstrated high intra-rater reliability [intraclass correlation coefficient (ICC)3,1 0.999, 95% confidence interval 0.996-1.000) and inter-rater reliability (ICC2,1 0.997, 95% confidence interval 0.992-0.999). The CMTInfS was able to discriminate between the CMT group and controls (P = 0.006), and convergent validity demonstrated good agreement between CMTInfS and CMTPedS scores (r = 0.76, P = 0.01). The final version of the CMTInfS requires 20 min to administer and is a reliable and sensitive functional outcome measure for early onset CMT and related neuropathies.10.1093/brain/awy280_video1awy280media15970672819001. [ABSTRACT FROM AUTHOR]

Endovascular clot retrieval (ECR) is an emerging therapy for treatment of acute ischaemic stroke (AIS) in adults, including basilar artery occlusion (BAO). Its role in children is not well established. We report four consecutive children with AIS due to BAO treated with ECR in Sydney, Australia. We reviewed the literature to characterize the 'natural course' of AIS due to BAO in children not treated with thrombolysis or ECR, and compared their outcome with our patients and reported children with BAO treated with ECR. Despite delays in diagnosis, ECR achieved recanalization in our four children. Three children had a good outcome (Paediatric Modified Rankin Score [PedmRS] 0-2). One child with acute leukaemia suffered recurrent basilar occlusion and died of brainstem dysfunction. Literature review identified 111 children exhibiting the natural course of AIS due to BAO, among whom 42% had good outcomes (PedmRS 0-2), 48% had significant residual disability (PedmRS 3-5), and 10% died. Of 34 children treated with ECR, 28 (82%) had good outcomes (PedmRS 0-2), five (15%) had significant residual disability (PedmRS 3-5), and one (3%) died. Complications of ECR were uncommon. These observations suggest ECR may be beneficial for children with AIS due to BAO. WHAT THIS PAPER ADDS: Children with acute ischaemic stroke (AIS) due to basilar artery occlusion (BAO) experience significant morbidity and mortality. Endovascular clot retrieval may be beneficial in children with AIS due to BAO. [ABSTRACT FROM AUTHOR]

Objective: Comprehensive clinical characterization of congenital titinopathy to facilitate diagnosis and management of this important emerging disorder.Methods: Using massively parallel sequencing we identified 30 patients from 27 families with 2 pathogenic nonsense, frameshift and/or splice site TTN mutations in trans. We then undertook a detailed analysis of the clinical, histopathological and imaging features of these patients.Results: All patients had prenatal or early onset hypotonia and/or congenital contractures. None had ophthalmoplegia. Scoliosis and respiratory insufficiency typically developed early and progressed rapidly, whereas limb weakness was often slowly progressive, and usually did not prevent independent walking. Cardiac involvement was present in 46% of patients. Relatives of 2 patients had dilated cardiomyopathy. Creatine kinase levels were normal to moderately elevated. Increased fiber size variation, internalized nuclei and cores were common histopathological abnormalities. Cap-like regions, whorled or ring fibers, and mitochondrial accumulations were also observed. Muscle magnetic resonance imaging showed gluteal, hamstring and calf muscle involvement. Western blot analysis showed a near-normal sized titin protein in all samples. The presence of 2 mutations predicted to impact both N2BA and N2B cardiac isoforms appeared to be associated with greatest risk of cardiac involvement. One-third of patients had 1 mutation predicted to impact exons present in fetal skeletal muscle, but not included within the mature skeletal muscle isoform transcript. This strongly suggests developmental isoforms are involved in the pathogenesis of this congenital/early onset disorder.Interpretation: This detailed clinical reference dataset will greatly facilitate diagnostic confirmation and management of patients, and has provided important insights into disease pathogenesis. Ann Neurol 2018;83:1105-1124. [ABSTRACT FROM AUTHOR]

Abstract: Background: Epileptic encephalopathies are a devastating group of neurological conditions in which etiological diagnosis can alter management and clinical outcome. Exome sequencing and gene panel testing can improve diagnostic yield but there is no cost‐effectiveness analysis of their use or consensus on how to best integrate these tests into clinical diagnostic pathways. Methods: We conducted a retrospective cost‐effectiveness study comparing trio exome sequencing with a standard diagnostic approach, for a well‐phenotyped cohort of 32 patients with epileptic encephalopathy, who remained undiagnosed after “first‐tier” testing. Sensitivity analysis was included with a range of commercial exome and multigene panels. Results: The diagnostic yield was higher for the exome sequencing (16/32; 50%) than the standard arm (2/32; 6.2%). The trio exome sequencing pathway was cost‐effective compared to the standard diagnostic pathway with a cost saving of AU$5,236 (95% confidence intervals $2,482; $9,784) per additional diagnosis; the standard pathway cost approximately 10 times more per diagnosis. Sensitivity analysis demonstrated that the majority of commercial exome sequencing and multigene panels studied were also cost‐effective. The clinical utility of all diagnoses was reported. Conclusion: Our study supports the integration of exome sequencing and gene panel testing into the diagnostic pathway for epileptic encephalopathy, both in terms of cost effectiveness and clinical utility. We propose a diagnostic pathway that integrates initial rapid screening for treatable causes and comprehensive genomic screening. This study has important implications for health policy and public funding for epileptic encephalopathy and other neurological conditions. [ABSTRACT FROM AUTHOR]

This paper focuses on the web of relationships established between Early and Middle Bronze Age communities and their environment in Northwest Iberia. Charcoal remains recovered from settlements and funerary sites in this area can inform a greater understanding of wood resource procurement and woodland management strategies adopted by these small-scale communities. Although charcoal analysis of contexts with chronologies ranging from 2200 to 1200 cal. BC is not commonly undertaken in this area, data from this period are of great importance because it represents a phase of major deforestation and landscape change. Wood resources were local and exploitation was conditioned by their availability in the environs of the sites. These communities established a clear preference for Quercus wood, combined recurrently with shrubby species of the Fabaceae family. This co-occurrence, previously observed in Middle and Late Bronze Age contexts, could extend back to the Early Bronze Age and even to the Late Neolithic. The presence of small trees and shrubs such as Rosaceae/Maloideae and Corylus avellana could be related with the open landscape that characterises this period, and with the existence of woodland management practices designed to prevent forest regeneration. [ABSTRACT FROM AUTHOR]

Survival of motor neuron 1-negative spinal muscular atrophy (SMA) is heterogeneous and remains a diagnostic challenge. The clinical spectrum continues to expand and 33 genes have been identified to date. The present report describes a 9-year-old girl with novel clinical phenotype of a patient with polyarticular arthritis followed by symptoms of SMA due to acid ceramidase deficiency. Whole exome sequencing identified compound heterozygous pathogenic mutation in the N-acylsphingosine amidohydrolase 1 gene. Functional assay with leukocyte acid ceramidase activity showed a decreased level in the proband confirming pathogenicity of the mutations. Mutations of N-acylsphingosine amidohydrolase 1 are known to separately cause Farber disease (arthritis, subcutaneous nodules, and dysphonia) or SMA with progressive myoclonic epilepsy. The present combined phenotype is novel, bringing together SMA with progressive myoclonic epilepsy and Farber disease and establishing a phenotypic spectrum. Acid ceramidase deficiency is an important consideration in patients presenting with polyarticular arthritis and motor neuron disease. [ABSTRACT FROM AUTHOR]

Introduction Peripheral nerve involvement is common in mitochondrial disease but often unrecognised due to the prominent central nervous system features. Identification of the underlying neuropathy may assist syndrome classification, targeted genetic testing and rehabilitative interventions. Methods Clinical data and the results of nerve conduction studies were obtained retrospectively from the records of four tertiary children's hospital metabolic disease, neuromuscular or neurophysiology services. Nerve conductions studies were also performed prospectively on children attending a tertiary metabolic disease service. Results were classified and analysed according to the underlying genetic cause. Results Nerve conduction studies from 27 children with mitochondrial disease were included in the study (mitochondrial DNA (mtDNA) – 7, POLG – 7, SURF1 – 10, PDHc deficiency – 3). Four children with mtDNA mutations had a normal study while three had mild abnormalities in the form of an axonal sensorimotor neuropathy when not acutely unwell. One child with MELAS had a severe acute axonal motor neuropathy during an acute stroke-like episode that resolved over 12 months. Five children with POLG mutations and disease onset beyond infancy had a sensory ataxic neuropathy with an onset in the second decade of life, while the two infants with POLG mutations had a demyelinating neuropathy. Seven of the 10 children with SURF1 mutations had a demyelinating neuropathy. All three children with PDHc deficiency had an axonal sensorimotor neuropathy. Unlike CMT, the neuropathy associated with mitochondrial disease was not length-dependent. Conclusions This is the largest study to date of peripheral neuropathy in genetically- classified childhood mitochondrial disease. Characterising the underlying neuropathy may assist with the diagnosis of the mitochondrial syndrome and should be an integral part of the assessment of children with suspected mitochondrial disease. [ABSTRACT FROM AUTHOR]

The endemic Azores Bullfinch or Priolo ( Pyrrhula murina ) is one of the most threatened European passerines, historically restricted to a single population in the Pico da Vara/Ribeira do Guilherme Special Protection Area (São Miguel Island, Azores, Portugal). Annual census of this species started in 1991. It usually took one observer 1–2 months to complete the census and even then, it was not logistically reasonable to include some areas with very steep slope in the core of the protected area. In order to bypass these constraints, an alternative and ambitious monitoring scheme that would allow estimating the whole species throughout its entire range was proposed in 2007. The new scheme, which complemented and improved previous estimates, consisted in performing a thorough instantaneous census using a distance sampling approach, thus allowing a detailed snapshot of effective occupation, density, habitat preferences and distribution range of the Azores Bullfinch. The Priolo Atlas turned into a volunteered geographic information and citizen science-based ornithological initiative which every 4 years congregates more than 50 well-trained volunteers in the Azores. With the first two editions (2008 and 2012), this initiative has already established itself as a critical tool to monitor the population of this endemic species. [ABSTRACT FROM AUTHOR]

The last remains of native laurel forest in the Azores are highly threatened by the spread of invasive plants. Because landslides are very frequent in these islands, conservation of native laurel forest requires knowledge of the patterns of bird-dispersed seed rain into forest gaps. We monitored 78 seed traps over 1 year to investigate (1) the role of perches in attracting avian dispersers into gaps, (2) temporal patterns in the dispersal of exotic and native seeds, (3) how seed rain affects vegetation establishment in gaps at different distances from the native forest and (4) whether the caloric content of fruits could explain the number of seeds dispersed. Perches were highly effective in concentrating avian seed dispersal. While some native fruits are produced all year-round, most exotic plants set fruits during the main peak of the native fruit production (August-November). Most seeds recovered from the traps were native, and native seed rain inside the native forest was higher than in gaps. However, deposition of exotic seeds was not affected by distance from native forest. Seed dispersal frequencies monitored by seed traps and by faecal analysis were correlated with each other, but not with fruit caloric content, suggesting that other factors are more important that the nutritional value in predicting avian fruit choice. Forest restoration activities should take into consideration that seed dispersal decreases sharply beyond 100 m from native forest and the attractive potential of perches to direct natural seed dispersal into forest gaps. [ABSTRACT FROM AUTHOR]

The article presents a study which investigates the variables that affect the spore phenology of two evergreen ferns Woodwardia radicans and Culcita macrocarpa in Sâo Miguel, Azores. The study used binomial distribution and Generalized Linear Models (GLMs) to determine the spore release date and maturation. The result indicates that the biotic pressures such as presence of spore feeders result in the long-term causes of the spore maturation and release of W. radicans and C. macrocarpa.

European grassland birds are experiencing major population declines, mainly due to changes in farmland management. We analyzed the role of habitat availability, grazing management and linear infrastructures (roads and power lines) in explaining spatial and temporal variation in the population density of little bustards (Tetrax tetrax) in Portugal, during a decade in which the species population size halved. We used data from 51 areas (totaling ca. 1,50,000 ha) that were sampled in two different periods (2003–2006 and 2016). In 2003–2006, when the species occurred at high densities, habitat availability was the only factor affecting spatial variation in bustard density. In the 2016 survey, variation in density was explained by habitat availability and livestock management, with reduced bird numbers in areas with higher proportions of cattle. Population declines across the study period were steeper in areas that initially held higher densities of bustards and in areas with a higher proportion of cattle in the total stocking rate. Areas with higher densities of power lines also registered greater density declines, probably due to avoidance behavior and to increased mortality. Overall, our results show little bustards are currently lacking high quality grassland habitat, whose persistence depends on extensive grazing regimes and low linear infrastructure densities. [ABSTRACT FROM AUTHOR]

• Near full-length genome analysis using next generation sequencing identified EV-A71 and other enterovirus A and B subtypes circulating. • The Sydney EV-A71 2013 strain was very similar to EV-A71 circulating in China and Vietnam during the previous year. • Strains causing more severe clinical manifestations grouped together phylogenetically. The most recent documented Australian outbreak of enterovirus A71 (EV-A71) occurred in Sydney from 2012 to 2013. Over a four-month period more than 100 children presented to four paediatric hospitals with encephalitic presentations including fever and myoclonic jerks. The heterogeneous presentations included typical encephalomyelitis, and cardiopulmonary complications. To characterise the genomes of enterovirus strains circulating during the 2013 Sydney EV-A71 outbreak and determine their phylogeny, phylogeography and association between genome and clinical phenotype. We performed an analysis of enterovirus (EV) positive specimens from children presenting to hospitals in the greater Sydney region of Australia during the 2013 outbreak. We amplified near full-length genomes of EV, and used next generation sequencing technology to sequence the virus. We used phylogenetic/phylogeographic analysis to characterize the outbreak viruses. We amplified and sequenced 23/63 (37 %) genomes, and identified the majority (61 %) as EV-A71. The EV-A71 sequences showed high level sequence homology to C4a genogroups of EV-A71 circulating in China and Vietnam during 2012-13. Phylogenetic analysis showed EV-A71 strains associated with more severe symptoms, including encephalitis or cardiopulmonary failure, grouped together more closely than those from patients with hand, foot and mouth disease. Amongst the non-EV-A71 sequences were five other EV subtypes (representing enterovirus subtypes A and B), reflecting the diversity of EV co-circulation within the community. This is the first Australian study investigating the near full-length genome of EV strains identified during a known outbreak of EV-A71. EV-A71 sequences were very similar to strains circulating in Asia during the same time period. Whole genome sequencing offers additional information over routine diagnostic testing such as characterisation of emerging recombinant strains and inform vaccine design. [ABSTRACT FROM AUTHOR]

Although the clinical use of targeted gene sequencing-based diagnostics is valuable, whole-exome sequencing has also emerged as a successful diagnostic tool in molecular genetics laboratories worldwide. Molecular genetic tests for episodic ataxia type 2 (EA2) usually target only the specific calcium channel gene (CACNA1A) that is known to cause EA2. In cases where no mutations are identified in the CACNA1A gene, it is important to identify the causal gene so that more effective treatment can be prioritized for patients. Here we present a case of a proband with a complex episodic ataxias (EA)/seizure phenotype with an EA-affected father; and an unaffected mother, all negative for CACNA1A gene mutations. The trio was studied by whole-exome sequencing to identify candidate genes responsible for causing the complex EA/seizure phenotype. Three rare or novel variants in Sodium channel α2-subunit; SCN2A (c.3973G>T: p.Val1325Phe), Potassium channel, Kv3.2; KCNC2 (c.1006T>C: p.Ser336Pro) and Sodium channel Nav1.6; SCN8A (c.3421C>A: p.Pro1141Thr) genes were found in the proband. While the SCN2A variant is likely to be causal for episodic ataxia, each variant may potentially contribute to the phenotypes observed in this family. This study highlights that a major challenge of using whole-exome/genome sequencing is the identification of the unique causative mutation that is associated with complex disease. [ABSTRACT FROM AUTHOR]