Subsea Maintenance Service Delivery:Mapping Factors Influencing Scheduled Service Duration

The oil and gas （O＆G） industry on the Norwegian continental shelf （NCS） leads the world in terms of the number of subsea O＆G installations. Ensuring the dependability of these assets is critical. Non-intrusive inspection, maintenance and repair （IMR） services are therefore needed to reduce risks. These services are planned and executed using a mono-hull offshore vessel complete with remotely operated vehicles （ROVs）, a module handling system and an active heave compensated crane. Vessel time is shared between competing jobs, using a prioritized forward-looking schedule. Extension in planned job duration may have an impact on O＆G production, service costs and health, safety, and environmental （HSE） risks. This paper maps factors influencing the job schedule efficiency. The influence factors are identified through reviews of literature as well as interviews with experts in one of the large IMR subsea service providers active on the Norwegian Continental Shelf. The findings show that the most obvious factors are weather disruption and water depth. Other factors include job complexity, job uncertainty, IMR equipment availability, as well as the mix of job complexity.

GDNF to the rescue:GDNF delivery effects on motor neurons and nerves,and muscle re-innervation after peripheral nerve injuries

Peripheral nerve injuries commonly occur due to trauma,like a traffic accident.Peripheral nerves get severed,causing motor neuron death and potential muscle atrophy.The current golden standard to treat peripheral nerve lesions,especially lesions with large(≥3 cm)nerve gaps,is the use of a nerve autograft or reimplantation in cases where nerve root avulsions occur.If not tended early,degeneration of motor neurons and loss of axon regeneration can occur,leading to loss of function.Although surgical procedures exist,patients often do not fully recover,and quality of life deteriorates.Peripheral nerves have limited regeneration,and it is usually mediated by Schwann cells and neurotrophic factors,like glial cell line-derived neurotrophic factor,as seen in Wallerian degeneration.Glial cell line-derived neurotrophic factor is a neurotrophic factor known to promote motor neuron survival and neurite outgrowth.Glial cell line-derived neurotrophic factor is upregulated in different forms of nerve injuries like axotomy,sciatic nerve crush,and compression,thus creating great interest to explore this protein as a potential treatment for peripheral nerve injuries.Exogenous glial cell line-derived neurotrophic factor has shown positive effects in regeneration and functional recovery when applied in experimental models of peripheral nerve injuries.In this review,we discuss the mechanism of repair provided by Schwann cells and upregulation of glial cell line-derived neurotrophic factor,the latest findings on the effects of glial cell line-derived neurotrophic factor in different types of peripheral nerve injuries,delivery systems,and complementary treatments(electrical muscle stimulation and exercise).Understanding and overcoming the challenges of proper timing and glial cell line-derived neurotrophic factor delivery is paramount to creating novel treatments to tend to peripheral nerve injuries to improve patients'quality of life.

Impact of prenatal,neonatal,and postnatal factors on epilepsy risk in children and adolescents:a systematic review and meta-analysis

Background Epilepsy is a common,long-term neurological condition.Several previous case-control,cohort and cross-sectional studies have highlighted the role of prenatal,delivery and postnatal factors in the onset of epilepsy.In this systematic review,we evaluate the impact of these factors on the development of epilepsy in children and adolescents.Methods We searched PubMed and Google Scholar for literature on the relationship between prenatal,delivery and postnatal factors and the occurrence of epilepsy.The research was performed according to the PRSIMA 2020 flowchart and checklist.Data were extracted and pooled according to the ReviewManager 5.3 software using a random-effects model.Sensitivity analysis and subgroup analysis were used to evaluate the source of heterogeneity.Results We identified 25 reports,including 45,044 cases with confirmed epilepsy and 2,558,210 controls.Premature birth is significantly associated with the risk of epilepsy(pooled OR=4.36[95%CI:1.26–15.09],P=0.02).Smoking during pregnancy significantly increases this risk by 28%(pooled OR=1.28[95%CI:1.1–1.49],P=0.002).Furthermore,maternal epilepsy confers a pooled OR of 2.06[95%CI:1.26–3.36].Eclampsia is linked to a 16.9-fold increased risk of epilepsy.In addition,both pregnancy metrorrhagia and maternal infection are significantly associated with the epilepsy risk(pooled OR=2.24[95%CI:1.36–3.71]and 1.28[95%CI:1.17–1.41],respectively).For delivery conditions,cord prolapse(pooled OR=2.58[95%CI:1.25–5.32]),prolonged labor(>6 h)(OR=6.74[95%CI:3.57–12.71])and head trauma(pooled OR=2.31[95%CI:1.54–3.48])represent a meaningful risk of epilepsy occurrence.Moreover,birth complications(OR=3.91[95%CI:2.43–6.29]),low birth weight(pooled OR=1.83[95%CI:1.5–2.23])and male birth(pooled OR=1.18[95%CI:1.06–1.32])are associated with an elevated risk of epilepsy in childhood and adolescence.Conclusions Epilepsy in children and adolescents can be attributed to a multitude of intricate factors,notably those during pregnancy,delivery and the postnatal period.These findings highlight the crucial role of prenatal and postnatal care in reducing the impact of these factors on epilepsy occurrence.

Photoactivated growth factor release from bio-orthogonally crosslinkedhydrogels for the regeneration of corneal defects

In situ-forming hydrogels are an attractive option for corneal regeneration, and the delivery of growth factorsfrom such constructs have the potential to improve re-epithelialization and stromal remodeling. However,challenges persist in controlling the release of therapeutic molecules from hydrogels. Here, an in situ-forming bioorthogonallycrosslinked hydrogel containing growth factors tethered via photocleavable linkages (PC-HAColhydrogel) was developed to accelerate corneal regeneration. Epidermal growth factor (EGF) was conjugated tothe hydrogel backbone through photo-cleavable (PC) spacer arms and was released when exposed to mild intensityultraviolet (UV) light (2–5 mW/cm2, 365 nm). The PC-HACol hydrogel rapidly gelled within a few minuteswhen applied to corneal defects, with excellent transparency and biocompatibility. After subsequentexposure to UV irradiation, the hydrogel promoted the proliferation and migration of corneal epithelial cells invitro. The rate of re-epithelialization was positively correlated to the frequency of irradiation, verified through exvivo rabbit cornea organ culture studies. In an in vivo rat corneal wound healing study, the PC-HACol hydrogelexposed to UV light significantly promoted re-epithelialization, the remodeling of stromal layers, and exhibitedsignificant anti-scarring effects, with minimal α-SMA and robust ALDH3A1 expression. Normal differentiation ofthe regenerated epithelia after healing was evaluated by expression of the corneal epithelial biomarker, CK12.The remodeled cornea exhibited full recovery of corneal thickness and layer number without hyperplasia of theepithelium.

Bone tissue engineering via growth factor delivery:from scaffolds to complex matrices

In recent years,bone tissue engineering has emerged as a promising solution to the limitations of current gold standard treatment options for bone related-disorders such as bone grafts.Bone tissue engineering provides a scaffold design that mimics the extracellular matrix,providing an architecture that guides the natural bone regeneration process.During this period,a new generation of bone tissue engineering scaffolds has been designed and characterized that explores the incorporation of signaling molecules in order to enhance cell recruitment and ingress into the scaffold,as well as osteogenic differentiation and angiogenesis,each of which is crucial to successful bone regeneration.Here,we outline and critically analyze key characteristics of successful bone tissue engineering scaffolds.We also explore candidate materials used to fabricate these scaffolds.Different growth factors involved in the highly coordinated process of bone repair are discussed,and the key requirements of a growth factor delivery system are described.Finally,we concentrate on an analysis of scaffold-based growth factor delivery strategies found in the recent literature.In particular,the incorporation of two-phase systems consisting of growth factor-loaded nanoparticles embedded into scaffolds shows great promise,both by providing sustained release over a therapeutically relevant timeframe and the potential to sequentially deliver multiple growth factors.

Molecular Tissue Engineering:Concepts,Status and Challenge

Tissue engineering has confronted many difficulties mainly as follows:1)How to modulate the adherence,proliferation,and oriented differentiation of seed cells, especially that of stemcells. 2) Massive preparation and sustained controllable delivery of tissue inducing factors or plasmid DNA, such as growth factors, angiogenesis stimulators,and so on. 3) Development of 'intelligent biomimetic materials' as extracellular matrix with a good superficial and structural compatibility as well as biological activity to stimulate predictable, controllable and desirable responses under defined conditions.Molecular biology is currently one of the most exciting fields of research across life sciences,and the advances in it also bring a bright future for tissue engineering to overcome these difficulties.In recent years,tissue engineering benefits a lot from molecular biology.Only a comprehensive understanding of the involved ingredients of tissue engineering (cells,tissue inducing factors,genes,biomaterials) and the subtle relationships between them at molecular level can lead to a successful manipulation of reparative processes and a better biological substitute.Molecular tissue engineering,the offspring of the tissue engineering and molecular biology,has gained an increasing importance in recent years.It offers the promise of not simply replacing tissue,but improving the restoration.The studies presented in this article put forward this new concept for the first time and provide an insight into the basic principles,status and challenges of this emerging technology.

An Overview of PRP-Delivering Scaffolds for Bone and Cartilage Tissue Engineering

Tissue engineering is nowadays an emerging approach that aims to replace or regenerate diseased or damaged organs with engineered constructs. Considering the key role of growth factors (GFs) in the tissue regeneration process, these biomolecules are considered an important part of the tissue engineering process, so the presence of growth factors in engineered scaffolds can accelerate tissue regeneration by influencing the behavior of cells. Platelet-rich plasma (PRP), as an autologous source of a variety of growth factors, is considered a therapeutic agent for the treatment of degenerative diseases. Regarding its ability to promote the healing process and tissue regeneration, PRP therapy has attracted great attention in bone and cartilage tissue engineering. Incorporating PRP and its derivatives into engineered scaffolds not only bioactivates the scaffold, but the scaffold matrix also acts as a sustained and localized growth factor release system. In addition, the presence of a scaffold can promote the bioactivity of GFs by providing an environment that facilitates their interaction, leading to enhanced effects compared to their free form. This review presents a brief overview of PRP's role in bone and cartilage tissue regeneration with the main focus on scaffold-mediated PRP delivery. In addition, the classification of platelet-rich products, current extraction techniques, terminology, and scaffold bioactivation methods are presented to provide a better understanding of the basics and the key aspects that may affect the effectiveness of therapy in bone and cartilage tissue engineering.

Specific bFGF targeting of KIM-1 in ischemic kidneys protects against renal ischemia-reperfusion injury in rats

Renal ischemia-reperfusion(I/R)injury is one of the major causes of acute kidney injury.However,there is still no effective treatment for this disease.Basic fibroblast growth factor(bFGF)has been reported to be beneficial for recovery from ischemic diseases.It is vital to increase the local concentration and reduce the diffusion of bFGF in vivo for renal I/R injury therapy.A targeted growth factor delivery system that responds to specific biological signals in the regenerative environment to guide release has been highlighted in tissue repair.In the present study,a specific peptide was fused with bFGF and called bFGF-kidney injury targeting(KIT-bFGF),and this compound specifically targeted kidney injury molecule-1 both in hypoxic renal HK-2 cells in vitro and ischemic kidneys in vivo after intravenous injection.When administered to rat models of renal I/R injury,KIT-bFGF attenuated renal tubule damage and fibrosis,and promoted functional recovery compared to the effects of native bFGF and the control.We also investigated the mechanism by which KIT-bFGF activated the ERK1/2 and Akt signaling pathways to significantly reduce apoptosis and protect against ischemic injury in the kidney.These results demonstrated that targeted delivery of KIT-bFGF could be an effective strategy for the treatment of renal I/R injury.