Hydraulic Fracturing at Clair: Unlocking the Potential of Europe's Largest Reservoir

The Greater Clair area, Europe's largest oilfield, has two existing platforms, Clair Phase 1 and Clair Ridge, on production with future potential for a third platform targeting undeveloped Lower Clair Group to the South of Ph1. Clair Phase 1 was the initial development of Clair, targeting Lower Clair Group (LCG) reservoir consisting of a complex Devonian sandstone in six units. Most Phase 1 wells penetrated relatively good quality reservoir enhanced by natural fractures, while more recently Clair Ridge wells took a similar approach targeting natural fractures, however that strategy is continually being evaluated. In some areas however low matrix quality and lack of natural fractures were the dominant characteristics resulting in lower production rates. A brief comparison of the range of production outcomes will be presented, including potential downsides of reliance on natural fractures. Given the large oil volumes in areas of known poorer rock quality, alongside variable production results, a hydraulic fracturing trial was initiated in 2017. Well 206/08-A23 (A23) targeted previously under-developed, poor-quality Unit VI within the Phase 1 Graben area where natural fractures are absent. A pre-frac production test established baseline production of 900BOPD in December 2018. The A23 objectives included subsequent hydraulically fracturing the well to test this techniques ability to unlock production from tight, matrix dominated formation. Detailed analysis of core, log and limited vertical well fracturing data (from initial fracturing trials of 1980's vintage), yielded robust designs. Key challenges included overcoming very low KV/KH ratios with fracture heights exceeding 300ft. The resulting detailed designs provided consistent and predictable hydraulic fracturing execution in A23 in 2019, including placement of four planned 500klbs treatments combined with coil clean-outs after each stage to unload solids and fluids from the well. Initial fracture designs were conservative in terms of pad and proppant scheduling which, alongside learnings around operational logistics offshore West of Shetlands and completion design, offer significant optimisations for future hydraulic fractures. Post frac A23 became the highest non-natural fractured producer across Clair. Initially a six-fold production increase was observed with monitoring of transient production ongoing. Tracer analysis confirmed production contribution from all zones. Proving fracturing technology brings opportunities to unlock poorer Phase 1 and Ridge reservoir areas. Additionally, significant portions of the undeveloped Lower Clair Group to the South of Ph1 comprises lower permeability reservoir with higher viscosity oil and reduced natural fracture presence. Hydraulic fracturing is therefore a crucial completion technique for developing this lower quality reservoir and brings significant value enhancement to the project. Efficient delivery of numerous large fractures in a harsh offshore environment West of Shetlands presents significant challenges. The influence of how the A23 fracturing results and learnings are guiding future hydraulic fracturing concept are detailed, including optimising platform engineering design to facilitate efficient fracturing operations while maintaining the required productivity in this challenging scenario.

Nanoscale Imaging and Analysis of Bone Pathologies

Understanding the properties of bone is of both fundamental and clinical relevance. The basis of bone’s quality and mechanical resilience lies in its nanoscale building blocks (i.e., mineral, collagen, non-collagenous proteins, and water) and their complex interactions across length scales. Although the structure–mechanical property relationship in healthy bone tissue is relatively well characterized, not much is known about the molecular-level origin of impaired mechanics and higher fracture risks in skeletal disorders such as osteoporosis or Paget’s disease. Alterations in the ultrastructure, chemistry, and nano-/micromechanics of bone tissue in such a diverse group of diseased states have only been briefly explored. Recent research is uncovering the effects of several non-collagenous bone matrix proteins, whose deficiencies or mutations are, to some extent, implicated in bone diseases, on bone matrix quality and mechanics. Herein, we review existing studies on ultrastructural imaging—with a focus on electron microscopy—and chemical, mechanical analysis of pathological bone tissues. The nanometric details offered by these reports, from studying knockout mice models to characterizing exact disease phenotypes, can provide key insights into various bone pathologies and facilitate the development of new treatments.

The WNT1G177C mutation specifically affects skeletal integrity in a mouse model of osteogenesis imperfecta type XV

The recent identification of homozygous WNT1 mutations in individuals with osteogenesis imperfecta type XV (OI-XV) has suggested that WNT1 is a key ligand promoting the differentiation and function of bone-forming osteoblasts. Although such an influence was supported by subsequent studies, a mouse model of OI-XV remained to be established. Therefore, we introduced a previously identified disease-causing mutation (G177C) into the murine Wnt1 gene. Homozygous Wnt1G177C/G177C mice were viable and did not display defects in brain development, but the majority of 24-week-old Wnt1G177C/G177C mice had skeletal fractures. This increased bone fragility was not fully explained by reduced bone mass but also by impaired bone matrix quality. Importantly, the homozygous presence of the G177C mutation did not interfere with the osteoanabolic influence of either parathyroid hormone injection or activating mutation of LRP5, the latter mimicking the effect of sclerostin neutralization. Finally, transcriptomic analyses revealed that short-term administration of WNT1 to osteogenic cells induced not only the expression of canonical WNT signaling targets but also the expression of genes encoding extracellular matrix modifiers. Taken together, our data demonstrate that regulating bone matrix quality is a primary function of WNT1. They further suggest that individuals with WNT1 mutations should profit from existing osteoanabolic therapies.

Alveolar socket healing in 5-lipoxygenase knockout aged female mice treated or not with high dose of zoledronic acid

This study investigated the role 5-lypoxigenase (5-LO) on alveolar socket healing in aged female mice treated with zoledronic acid (ZL). Forty 129/Sv female mice (64–68 weeks old), 20 wild type (WT) and 20 5-LO knockout (5LOKO) were equally distributed according to ZL treatment: WT Control, WT ZL, 5LOKO Control, and 5LOKO ZL. ZL groups were treated with an intraperitoneal injection of 250 µg/Kg of ZL, while controls were treated with saline. Treatments were administered once a week, starting four weeks before surgery for tooth extraction and until 7 and 21 days post-surgery. Mice were euthanized for a comprehensive microscopic analysis (microCT, histomorphometry and immunohistochemistry). WT ZL mice presented intense inflammatory infiltrate (7 days), delayed bone formation (21 days), reduced collagenous matrix quality, and a deficiency in Runx-2 + , TRAP + , and macrophages as compared to controls. 5LOKO ZL animals presented decreased number of Runx-2 + cells in comparison to 5LOKO Control at 7 days, but no major changes in bone healing as compared to WT or 5LOKO mice at 21 days. The knockout of 5LO favored intramembranous bone healing in aged female mice, with a direct impact on inflammatory response and bone metabolism on the development of ONJ-like lesions.

Direct Perfusion Improves Redifferentiation of Human Chondrocytes in Fibrin Hydrogel with the Deposition of Cartilage Pericellular Matrix

Articular cartilage has limited potential for self-repair, and cell-based strategies combining scaffolds and chondrocytes are currently used to treat cartilage injuries. However, achieving a satisfying level of cell redifferentiation following expansion remains challenging. Hydrogels and perfusion bioreactors are known to exert beneficial cues on chondrocytes; however, the effect of a combined approach on the quality of cartilage matrix deposited by cells is not fully understood. Here, we combined soluble factors (BMP-2, Insulin, and Triiodothyronine, that is, BIT), fibrin hydrogel, direct perfusion and human articular chondrocytes (HACs) to engineer large cartilage tissues. Following cell expansion, cells were embedded in fibrin gels and cultivated under either static or perfusion conditions. The nature of the matrix synthesized was assessed by Western blotting and immunohistochemistry. The stability of cartilage grafts and integration with native tissue were also investigated by subcutaneous implantation of human osteochondral cylinders in nude mice. Perfusion preconditioning improved matrix quality and spatial distribution. Specifically, perfusion preconditioning resulted in a matrix rich in type II collagen but not in type I collagen, indicating the reconstruction of hyaline cartilage. Remarkably, the production of type VI collagen, the main component of the pericellular matrix, was also increased, indicating that chondrocytes were connecting to the hyaline matrix they produced.

Matrix quality determines the strength of habitat loss filtering on bird communities at the landscape scale

Habitat loss and fragmentation represent a major threat to biodiversity, however, the modulation of its effects by the non-habitat matrix surrounding habitat patches is still undervalued. The landscape matrix might change community assembly in different ways. For example, low-quality matrices can accentuate environmental filtering by reducing resource availability and/or deteriorating abiotic conditions but they may also over limit dispersal of organisms and make communities more prone to ecological drift. To understand how matrix quality modulates the effects of habitat loss, we quantified the relative importance of environmental filter and ecological drift in bird occurrences across both local and landscape gradients of habitat loss embedded in low- and high-quality matrices. We used a trait-based approach to understand habitat loss filtering effects on birds. We found that low-quality matrices, composed mainly of low-productive pasturelands, increased the severity of habitat loss filtering effects for forest specialist birds, but only at the landscape scale. Bird occurrence was in general higher in high-quality matrices, i.e., more heterogeneous and with low-contrasting edges, indicating the role of the matrix quality on attenuating species extinction risks at the landscape scale probably due to mass effect. Moreover, forest specialists presented a strong negative response to habitat loss filtering across different functional traits, while generalists presented a high variability in traits response to habitat loss. We raised evidence in supporting that landscape habitat loss filtering may be relaxed or reinforced depending on the quality of the matrix, evidencing that matrix quality has a strong impact in modulating community assembly processes in fragmented landscapes. In practical terms, it means that improving matrix quality may help in maintaining the high diversity of birds even without any increase in native forest cover.

Human Acellular Amniotic Matrix with Previously Seeded Umbilical Cord Mesenchymal Stem Cells Restores Endometrial Function in a Rat Model of Injury

Background. Abnormal endometrial repair after injury results in the formation of intrauterine adhesions (IUA) and a thin endometrium, which are key causes for implantation failure and infertility. Stem cell transplantation offers a potential alternative for some cases of severe Asherman’s syndrome that cannot be treated with surgery or hormonal therapy. Umbilical cord-derived mesenchymal stem cells (UCMSCs) have been reported to repair the damaged endometrium. However, there is no report on the effects of UCMSCs previously seeded on human acellular amniotic matrix (AAM) on endometrial injury. Methods. Absolute ethanol was injected into rat uteri to damage the endometrium. UCMSCs previously seeded on AAM were surgically transplanted. Using a variety of methods, the treatment response was assessed by endometrial thickness, endometrial biomarker expression, endometrial receptivity, cell proliferation, and inflammatory factors. Results. Endometrial thickness was markedly improved after UCMSC-AAM transplantation. The expression of endometrial biomarkers, namely, vimentin, cytokeratin, and integrin β3, in treated rats increased compared with untreated rats. In the UCMSC-AAM group, the VEGF expression decreased, whereas that of MMP9 increased compared with the injury group. Moreover, in the AAM group, the MMP9 expression increased. The expression of proinflammatory factors (IL-2, TNFα, and IFN-γ) in the UCMSC-AAM group decreased compared with the untreated group, whereas the expression of anti-inflammatory factors (IL-4, IL-10) increased significantly. Conclusions. UCMSC transplantation using AAM as the carrier can be applied to treat endometrial injury in rats. The successful preparation of lyophilized AAM provides the possibility of secondary infectious disease screening and amniotic matrix quality detection, followed by retrospective analysis. The UCMSC-AAM complex may promote the better application of UCMSCs on the treatment of injured endometrium.

Chemometric Differentiation of Pistachios (Pistacia vera, Greek ‘Aegina’ Variety) from Two Different Harvest Years Using FTIR Spectroscopy and DRIFTS and Disk Techniques

Food quality is a topic of utmost importance as more and more emphasis is placed on quality rather than quantity of products. Previous studies have pointed out the interaction of quality with the harvest year. In this study, 22 Pistacia vera (Greek ‘Aegina’ variety) samples (11 from 2017 and 11 from 2018) were differentiated using Fourier transform infrared spectroscopy (FTIR) and (a) diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) and (b) KBr/sample disk techniques. In both years, the pistachios trees’ growing followed standard cultivation methods and similar agronomic conditions. Two chemometric models were developed using partial least squares-discrimination analysis (PLS-DA). DRIFTS proved unable to statistically differentiate the samples (R2 = 0.96266, Q2 = 0.63152). On the contrary, the disk technique completely differentiated the pistachio samples (R2 = 0.99705, Q2 = 0.97719). The 1720–1800 cm−1 region mostly contributed to the discrimination. The disk-FTIR chemometric model is fast, robust, economical, and environmentally friendly for determining pistachio matrix quality.