Marine litter is a pollution problem affecting thousands of marine species in all the world's seas and oceans. Marine litter, in particular plastic, has negative impacts on marine wildlife primarily ...due to ingestion and entanglement. Since most marine mammal species negatively interact with marine litter, a first workshop under the framework of the European Cetacean Society Conference, was held in 2017 to bring together the main experts on the topic of marine mammals and marine litter from academic and research institutes, non-governmental organisations, foundations and International Agreements. The workshop was devoted to defining the impact of marine litter on marine mammals by reviewing current knowledge, methodological advances and new data available on this emerging issue. Some case studies were also presented from European waters, such as seals and cetaceans in the North, Baltic, and Mediterranean Seas. Here, we report the main findings of the workshop, including a discussion on the research needs, the main methodological gaps, an overview of new techniques for detecting the effects of marine litter (including microplastics) on marine mammals and, also, the use of citizen science to drive awareness. The final recommendations aim to establish priority research, to define harmonised methods to detect marine litter and microplastics, enforce networking among institutions and support data sharing. The information gathered will enhance awareness and communication between scientists, young people, citizens, other stakeholders and policy makers, and thereby facilitate better implementation of international directives (e.g., the Marine Strategy Framework Directive) in order to answer the question about the actual status of our oceans and finding solutions.
•Harmonised protocols are needed to define the amount of ingested debris that can cause negative effects.•Protocols to evaluate the presence and effects of micro and nanoplastics should be further developed.•Methods to evaluate the exposure to plastics and plastic additives in free-ranging organisms are required.•Communicating to scientists, citizens, stakeholders and policy makers to enhance awareness raising.•A consistent monitoring approach is required, as marine litter pollution is estimated to increase.
To understand the sources, the transfer and the effects of marine litter, and therefore their impacts on marine mammal researchers need to apply a multidisciplinary standardized protocols.
von Willebrand disease (VWD) is the most common inherited bleeding disorder, and type 1 VWD is the most common VWD variant. Despite its frequency, diagnosis of type 1 VWD remains the subject of ...debate. In order to study the spectrum of type 1 VWD in the United States, the Zimmerman Program enrolled 482 subjects with a previous diagnosis of type 1 VWD without stringent laboratory diagnostic criteria. von Willebrand factor (VWF) laboratory testing and full-length VWF gene sequencing was performed for all index cases and healthy control subjects in a central laboratory. Bleeding phenotype was characterized using the International Society on Thrombosis and Haemostasis bleeding assessment tool. At study entry, 64% of subjects had VWF antigen (VWF:Ag) or VWF ristocetin cofactor activity below the lower limit of normal, whereas 36% had normal VWF levels. VWF sequence variations were most frequent in subjects with VWF:Ag <30 IU/dL (82%), whereas subjects with type 1 VWD and VWF:Ag ≥30 IU/dL had an intermediate frequency of variants (44%). Subjects whose VWF testing was normal at study entry had a similar rate of sequence variations as the healthy controls (14%). All subjects with severe type 1 VWD and VWF:Ag ≤5 IU/dL had an abnormal bleeding score (BS), but otherwise BS did not correlate with VWF:Ag. Subjects with a historical diagnosis of type 1 VWD had similar rates of abnormal BS compared with subjects with low VWF levels at study entry. Type 1 VWD in the United States is highly variable, and bleeding symptoms are frequent in this population.
•Type 1 VWD in the United States is highly variable, including patients with very low VWF levels as well as those with mild or minimal VWF deficiency.•The frequency of sequence variants in the VWF gene increases with decreasing VWF level, but BS does not vary by VWF level.
Marine debris is one of the most significant problems facing the marine environment, endangering wildlife, polluting oceans and is an issue which holds global significance. Plastics constitute a ...large proportion of marine debris, and their persistence can cause a number of negative consequences for biota and the environment, including entanglement and ingestion, which can lead to mortality. Most plastics never biodegrade and instead break down into smaller pieces which are more difficult to monitor and eventually become so small (micro and nanoplastics), that they are challenging to observe or intercept in the ocean. Marine-based Research Infrastructures (RIs) monitor several environmental parameters and are situated around the globe; however, none of these are routinely monitoring marine debris or plastics. Currently, the only infrastructures in place with regard to marine debris are 'physical debris interception infrastructure' in the form of barriers constructed to prevent marine debris from entering the ocean. Several knowledge gaps and restraints exist within current in situ infrastructure including technological immaturity, diverse methodologies and lack of data harmonisation. Nevertheless, marine RIs could monitor microplastics within the water column on a long-term basis and initial steps towards developing technology are promising.
Diagnosis and classification of VWD is aided by molecular analysis of the VWF gene. Because VWF polymorphisms have not been fully characterized, we performed VWF laboratory testing and gene ...sequencing of 184 healthy controls with a negative bleeding history. The controls included 66 (35.9%) African Americans (AAs). We identified 21 new sequence variations, 13 (62%) of which occurred exclusively in AAs and 2 (G967D, T2666M) that were found in 10%-15% of the AA samples, suggesting they are polymorphisms. We identified 14 sequence variations reported previously as VWF mutations, the majority of which were type 1 mutations. These controls had VWF Ag levels within the normal range, suggesting that these sequence variations might not always reduce plasma VWF levels. Eleven mutations were found in AAs, and the frequency of M740I, H817Q, and R2185Q was 15%-18%. Ten AA controls had the 2N mutation H817Q; 1 was homozygous. The average factor VIII level in this group was 99 IU/dL, suggesting that this variation may confer little or no clinical symptoms. This study emphasizes the importance of sequencing healthy controls to understand ethnic-specific sequence variations so that asymptomatic sequence variations are not misidentified as mutations in other ethnic or racial groups.
The diagnosis of von Willebrand disease relies on abnormalities in specific tests of von Willebrand factor (VWF), including VWF antigen (VWF:Ag) and VWF ristocetin cofactor activity (VWF:RCo). When ...examining healthy controls enrolled in the T. S. Zimmerman Program for the Molecular and Clinical Biology of von Willebrand disease, we, like others, found a lower mean VWF:RCo compared with VWF:Ag in African American controls and therefore sought a genetic cause for these differences. For the African American controls, the presence of 3 exon 28 single nucleotide polymorphisms (SNPs), I1380V, N1435S, and D1472H, was associated with a significantly lower VWF:RCo/VWF:Ag ratio, whereas the presence of D1472H alone was associated with a decreased ratio in both African American and Caucasian controls. Multivariate analysis comparing race, SNP status, and VWF:RCo/VWF:Ag ratio confirmed that only the presence of D1472H was significant. No difference was seen in VWF binding to collagen, regardless of SNP status. Similarly, no difference in activity was seen using a GPIb complex-binding assay that is independent of ristocetin. Because the VWF:RCo assay depends on ristocetin binding to VWF, mutations (and polymorphisms) in VWF may affect the measurement of “VWF activity” by this assay and may not reflect a functional defect or true hemorrhagic risk.
To assess the safety and efficacy of a fixed dose of recombinant activated factor VII (rFVIIa; NovoSeven) in the home setting for mild to moderately severe joint, muscle; and mucocutaneous bleeding ...episodes in patients with haemophilia A or B with inhibitors.
Multicentre, open-label, single arm, phase III study of one year duration. METHODS; Patients or their caregivers administered up to three doses of rFVIIa (90 microg/kg i.v.) at 3 h intervals within 8 h of the onset of a mild to moderate bleeding episode. Once the subject considered that rFVIIa had been "effective" with regard to haemostasis (after 1-3 injections), one further (maintenance) dose of rFVIIa was administered.
Of 60 patients enrolled, 56 experienced at least one bleed, and 46 completed the one year study. 614 of 877 bleeds (70%) were evaluable according to protocol definitions. Haemostasis was rated as "effective" in 92% (566/614) of evaluable bleeds after a mean of 2.2 injections. For successfully treated episodes, the time from onset of bleeding until administration of the first injection was 1.1+/-2.0 h (mean+/-SD). Twenty-four hours after initial successful response, haemostasis was reported as having been maintained in 95% of cases. Efficacy was comparable for muscle, joint and target joint, and mucocutaneous bleeding episodes. In an intent-to-treat analysis of all 877 bleeding events, efficacy outcomes were equivalent to the evaluable bleeds, with an effective response in 88% of treated episodes. Treatment-related adverse events occurred in 32 (3% of all) bleeding episodes and consisted of re-bleeds/new bleeds in more than 50% (18/32) of these events. A single episode of superficial thrombophlebitis was the only thrombotic complication encountered, and there were no patient withdrawals due to adverse events. Development of FVII(a) antibodies could not be detected, and hypersensitivity reactions to rFVIIa were not reported.
rFVIIa is effective and well tolerated when used in the home setting to treat mild to moderate bleeding episodes in patients with haemophilia A or B with inhibitors.
Recombinant human FIX (rFIX) was evaluated in 28 subjects, including 26 with mild, moderate, or severe haemophilia B and two haemophilia B carriers undergoing 36 surgical procedures. Preoperative ...rFIX dose was highly correlated with postinfusion FIX activity, r=0.61, P=0.0158. Peri‐ and post‐operative estimated blood loss was similar to that expected in non‐haemophilic individuals, and haemostasis was rated as excellent or good in 34 of 35 (97.1%) of the operative procedures. Transfusions were required in five of 36 (13.9%) procedures, including one liver transplantation, and three knee and one hip arthroplasties. Adverse events occurred in 15 of 28 (53.6%) subjects, but there were no perioperative haemorrhages, thromboembolic events, coagulation activation, viral transmission, or inhibitor formation. A transient low‐responding FIX inhibitor developed in one subject preoperatively, but required no change in treatment and resolved 15 months later. Thus, rFIX was found to be safe and effective in achieving haemostasis in subjects with FIX deficiency undergoing surgery.
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