High Risk Of Failure Research Articles

The role of external-beam radiotherapy for differentiated thyroid cancer.

The treatment options for differentiated thyroid cancer (DTC) are surgery, thyroid stimulating hormone suppression, radioactive iodine, and multitargeted tyrosine kinase inhibitors. The role of external-beam radiotherapy (EBRT) for DTC is controversial because of the lack of randomized controlled trials, but prospective single-arm studies and propensity score matching analyses have shown its efficacy and safety. This review discusses the role of EBRT after resection of gross disease, when there is a high risk of locoregional failure, as well as its role for locoregionally gross recurrent and unresectable disease. As in other tumor sites, EBRT has an important role in the palliative management and local control of patients with metastatic DTC, especially with bone and brain metastases.

Priority-based QoS Extensions and IAM Improvements

The command and control system operates in a harsh and dynamic environment with limited resources and have a very high risk of failure or malfunction. In the case of military information systems, including the command and control system, the efficiency and effectiveness of system resource management are very important and required. Therefore, the application of a QoS-like approach is necessary to improve the operational effectiveness of all command and control system resources. However, supporting QoS at the entire command and control system level incurs additional costs and burdens for implementation and operation. This paper describes the necessity and possibility of collaboration with QoS and IAM (identity and access management) among the collaboration between core functions within the command and control system. This paper proposes an extended QoS approach to improve the operational effectiveness of the entire command and control system resources. As a result of this research, expanded concepts, structures, standards, and methods of collaboration between QoS and IAM are developed and presented, and their feasibility is demonstrated through prototype development and experiments.

Contribution to the design of prestressed hollow core purlins without transverse reinforcement

AbstractThe hollow core purlin is a structural element resulting from the sectioning of hollow core slabs into two ribs. This component can be classified as a prestressed hollow core beam without transverse reinforcement. Although this solution offers potential for increasing the productivity of precast concrete element factories, it currently lacks normative guidelines due to the high risk of shear failure. The aim of this study is to highlight an equation to underpin the design of hollow core purlins based on experimental verification. To achieve this objective, six samples of hollow core purlins were analyzed. Initially, the manufacturing characteristics and cross‐sectional geometry of each piece were observed to gather data on the production process. Subsequently, positive bending tests were conducted to characterize stiffness and determine the effective mean tensile strength. Later, shear strength tests were performed to identify the failure mechanisms of the elements. In parallel, the prestressing forces, stiffness, tensile strength, cracking moment, calculated shear strength using the flexural‐shear mechanism, and verification of shear strength due to diagonal tension were computed based on concrete compressive strength values and data provided by the manufacturer. Finally, the experimental values obtained were compared with the theoretical calculated values to establish a correlation that highlights the calculation procedure that best represents the behavior of the studied elements.

The Potential Role of Cigarette Smoke, Elastic Fibers, and Secondary Lung Injury in the Transition of Pulmonary Emphysema to Combined Pulmonary Fibrosis and Emphysema

Combined pulmonary fibrosis and emphysema (CPFE) is a distinct syndrome associated with heavy smoking. The fibrotic component of the disease is generally believed to be superimposed on previously existing pulmonary emphysema, but the mechanisms responsible for these changes remain poorly understood. To better understand the pathogenesis of CPFE, we performed a series of experiments that focused on the relationships between lung elastic fibers, cigarette smoke, and secondary lung injury. The results indicate that even brief smoke exposure predisposes the lung to additional forms of lung injury that may cause alveolar wall fibrosis. The proinflammatory activity of smoke-induced structural alterations in elastic fibers may contribute to this process by enhancing secondary lung inflammation, including acute exacerbations of chronic obstructive pulmonary disease. Furthermore, the levels of the unique elastin crosslinks, desmosine and isodesmosine, in blood, urine, and sputum may serve as biomarkers for the transition from pulmonary emphysema to interstitial fibrosis. While the long-term effects of these inflammatory reactions were not examined, the current studies provide insight into the potential relationships between elastic fiber injury, cigarette smoke, and secondary lung injury. Determining the mechanisms involved in combined pulmonary emphysema and fibrosis and developing a sensitive biomarker for this type of lung injury may permit timely therapeutic intervention that could mitigate the high risk of respiratory failure associated with this condition.

Corneal Artificial Endothelial Layer (EndoArt): Literature Review and Our Experience

Background/Objectives: The objective of this study was to examine the morphological corneal changes and outcomes following the implantation of an artificial endothelial layer (EndoArt) in patients with chronic corneal oedema. Methods: A systematic review of the literature was conducted alongside a detailed analysis of two clinical cases with chronic corneal oedema that were treated using EndoArt. Our experience with these two cases is included to provide practical insights and real-world outcomes. Results: Across the 24 cases reported (including the two presented here), an analysis was possible in 23 cases. Notably, 82% of patients had undergone at least one previous corneal transplant, with 39% having undergone three or more transplants. Additionally, 78% of cases had ocular comorbidities, with glaucoma surgery being the most prevalent (83%), which could have impacted visual outcomes. The follow-up period ranged from 3 to 17 months with a median of 3 months. After EndoArt implantation, the average reduction in the central corneal thickness (CCT) was 29%, and the rebubbling rate was 47.8%, with some cases requiring no rebubbling, while others required it up to 100% of the time. Visual acuity significantly improved from a mean best-corrected visual acuity (BCVA) value of 1.61 ± 0.5 logMAR to 1.07 ± 0.59 logMAR (p < 0.001). The CCT decreased from 771 ± 146 µm to 580 ± 134 µm (p < 0.001). These findings are consistent with our experience. Conclusions: EndoArt shows promise as an alternative treatment for chronic corneal oedema in complex cases where conventional corneal transplantation has failed or carries a high risk of failure. The morphological changes observed using anterior segment optical coherence tomography (OCT) and in vivo confocal microscopy (IVCM) were similar to those reported after endothelial keratoplasty, with the notable exception of the absence of the hyper-reflective donor–host interface.

Corneal Endothelial Keratoprosthesis EndoArt in Patients with Glaucoma at High Risk of Graft Failure After Keratoplasty.

The novel endothelial keratoprosthesis EndoArt improves corneal edema by reducing the inflow of aqueous humor into the cornea. We assessed the early outcome after EndoArt implantation in patients at a high risk of graft failure after keratoplasty. This retrospective study included 14 patients with high-risk eyes owing to at least one of the following risk factors for graft failure after keratoplasty: multiple previous surgeries (glaucoma surgery, keratoplasty) and recurrent intraocular inflammation because of uveitis, aniridia, or anterior synechia. After descemetorhexis, the EndoArt keratoprosthesis was placed on the posterior stroma, secured with a gas bubble and 1 to 3 transcorneal holding sutures. Best spectacle-corrected visual acuity and central corneal thickness were calculated preoperatively and postoperatively. In addition, detachment of the keratoprosthesis and the need for additional gas injections (rebubbling) were analyzed. Octafluoropropane (C3F8) 12% in 11 patients and sulfur hexafluoride 20% in 3 patients were used to attach EndoArt. Detachments requiring at least 1 rebubbling occurred in 8 eyes. Preoperative best spectacle-corrected visual acuity was 1.6 (±0.6) logarithm of the minimal angle of resolution and improved to 1.3 (±0.6) after 12 weeks. Preoperative central corneal thickness (771.8 μm ± 157) significantly decreased postoperatively in all patients (622.1 μm ± 184.7 [P = 0.025] and 562.8 μm ± 183.6 [P = 0.012] after 6 and 12 weeks, respectively). EndoArt improved visual acuity and significantly reduced corneal thickness within 3 months postoperatively, subjectively, but not statistically significantly. The rebubbling rates in this cohort with an altered anterior segment anatomy were relatively high. Patients at a high risk of graft failure may benefit from this novel endothelial keratoprosthesis.

High-Intensity interval training improves global longitudinal strain in patients with metabolic syndrome and high risk of heart failure

Abstract Background Metabolic syndrome (MS) has been associated with the development of myocardial dysfunction which can lead to heart failure (HF). It is possible to detect early signs of myocardial dysfunction by assessing the global longitudinal strain (GLS) in a transthoracic echocardiography. A reduced GLS is considered as a predictor of HF development. Preventive strategies are recommended in patients with MS to avoid the progression to HF. Although exercise improves cardiovascular and metabolic health in MS patients, it is unknown whether exercise can affect the evolution of GLS in a group of patients with MS who are under medical treatment. Purpose To assess the prevalence of myocardial dysfunction (i.e., reduced GLS) in a heterogeneous group of patients with MS who are under medical treatment, and to test in these patients if 16 weeks of high-intensity interval training (HIIT) can improve the GLS. Methods Seventy-seven volunteers with MS and without signs or symptoms of HF were randomized in one of two 16-week intervention: i). HIIT in stationary bikes 3 sessions/week, 50 minutes/session + medical treatment (HIIT group), or ii). medical treatment (CONTROL). Maximal oxygen consumption (VO2max), and GLS together with rutinary echocardiographic parameters were assessed before and after intervention. The effect of HIIT compared to CONTROL was analyzed by a split-plot ANOVA to compare the effects of time (pre vs. post) and group (HIIT vs. CONTROL), and the interaction between the two factors. Results Before intervention 48.9% of participants from the HIIT group, and 46.7% from the CON group had a reduced GLS (i.e., >17% for men and >18% for women). However, none of them had a reduced left ventricular ejection fraction (LVEF), signs of diastolic dysfunction or an abnormal VO2max (less than 80% of predicted VO2max). After the 16-week intervention, only individuals from the HIIT group improved their VO2max (time*group P<0.001). LVEF did not improve in any of the experimental groups (time P=0.278) HIIT group improved their GLS by 0.51%, whereas CONTROL group improved it by 0.05% without reaching statistical significance (time*group P=0.186). However, a subgroup analysis of GLS conducted among the participants from the HIIT group discriminated by their pre-intervention values (GLS normal or reduced), showed that individuals with reduced GLS improved significantly by 1,41% (P=0.001) whereas those with a normal GLS improved by 0.14% without reaching statistical significance (P=0.736, time*group P=0.009). Conclusions Myocardial dysfunction assessed by GLS is present in MS even in the absence of symptoms, diastolic dysfunction, or reductions in the LVEF. HIIT can reduce the risk of HF development by improving GLS in patients with MS and early signs of myocardial dysfunction.A. Overall changes in GLSB. Subgroup analysis of GLS pre vs. post

Exome sequencing in over 63,000 patients in TIMI trials uncovers pathogenic cardiomyopathy variant carriers with high risk for heart failure and cardiovascular death

Abstract Background Rare genetic variants predisposing to cardiomyopathy (CMP) confer increased risk for adverse events. The prevalence of CMP variants in contemporary cardiovascular (CV) trials and their association with prevalent heart failure (HF) and incident HF hospitalizations (HHF) is not established. Purpose We aimed to identify carriers of rare pathogenic/likely pathogenic (PLP) variants for dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), and arrhythmogenic right ventricular cardiomyopathy (ARVC) in well-phenotyped clinical trial cohorts and to evaluate their prognostic significance. Methods Rare variants were identified from high-quality exome sequencing data from 5 large clinical trials (ENGAGE AF-TIMI 48, SAVOR-TIMI 53, PEGASUS-TIMI 54, DECLARE-TIMI 58, FOURIER (TIMI 59)). Putatively pathogenic variants for cardiomyopathy were identified using phenotype- and gene-specific curation of protein-truncating variants and high-confidence variant classifications from ClinVar. We conducted logistic regression for prevalent disease and Cox proportional hazard models for incident HHF, both adjusted by age, sex, trial, and first 10 principal components and using those without CMP variants as the reference. Sensitivity analysis by history of HF at baseline was performed for prospective outcomes. Results In 63,700 participants, we identified 866 CMP variant carriers of which 518 identified as DCM carriers (age 65±9 yrs, male 66%), 194 HCM carriers (65.5±9 yrs, male 69%), and 125 ARVC carriers (66±9 yrs, male 77%). Out of the 518 DCM variant carriers, 402 had a PLP variant in TTN. DCM variant carriers had higher odds of history of HF (Odds ratio [OR] 1.94, 1.57-2.39, p<0.0001) whereas this was not observed for HCM variant carriers (OR 1.18, 0.85-1.65, p=0.33) or ARVC variant carriers (OR 1.23, 0.80-1.90, p=0.35). Over a mean follow-up of 2.5 years, the rate of HHF was significantly higher for DCM variant carriers (Hazard ratio [HR] 1.58, 1.14-2.20, p=0.006), HCM variant carriers (HR 2.78, 1.87-4.13, p<0.001), and ARVC variant carriers (HR 1.89, 1.02-3.53, p=0.04). These associations were, if anything, stronger in patients without HF at baseline (HR 2.06, 1.30-3.25) than in patients with HF at baseline (HR 1.48, 1.12-1.95). DCM variant carriers also had a higher rate of CV death (HR 1.50, 1.05-2.12, p=0.02), which was not observed for HCM (HR 1.10, 0.57-2.11, p=0.78) or ARVC (HR 0.35, 0.09-1.41, p=0.14) variant carriers. Conclusion In 5 contemporary CV trials, CMP variant carriers have an increased rate of HHF, while DCM variant carriers also have a higher rate of CV death. These findings motivate better identification of these high-risk individuals and the incorporation of genetic testing in CV trials.

Design of a Bionic Spider Robot with a Two-Degrees-of-Freedom Leg Structure and Body Frame

Spiders have unique biological characteristics and excellent maneuverability, making them an ideal model for bionic robot design. However, traditional bionic spider robot designs usually have multiple degrees of freedom and confront many challenges. These challenges include complex control requirements, higher energy consumption, larger size and weight, higher risk of failure, and higher cost. This study proposes a leg design with two degrees of freedom to reduce its control and manufacturing costs. It can better control leg movement and improve leg force through a multi-link mechanism and a dual-motor system. In addition, the triangular gait and hexagonal body structure align the weight of the body with the support point, thereby enhancing stability. This study offers a comprehensive and organized approach to bio-inspired robot design, providing a valuable reference for future bionic robot development.

Atrasentan in Patients with IgA Nephropathy.

Patients with IgA nephropathy and severe proteinuria have a high lifetime risk of kidney failure. The efficacy and safety of the selective endothelin type A receptor antagonist atrasentan in reducing proteinuria in patients with IgA nephropathy are incompletely understood. We are conducting a phase 3, multinational, double-blind, randomized, controlled trial involving adults with biopsy-proven IgA nephropathy, a total urinary protein excretion of at least 1 g per day, and an estimated glomerular filtration rate of at least 30 ml per minute per 1.73 m2 of body-surface area. Patients were randomly assigned to receive atrasentan (0.75 mg per day) or matched placebo for 132 weeks. The primary outcome, assessed at a prespecified interim analysis of data from the first 270 patients in the main stratum, was the change in the 24-hour urinary protein-to-creatinine ratio from baseline to week 36; the change was estimated with the use of a repeated-measures model. (An exploratory stratum of patients who were receiving a sodium-glucose cotransporter 2 inhibitor were included in a separate analysis.) Safety analyses were based on adverse events across the entire main stratum. A total of 340 patients were recruited into the main stratum. Among the first 270 patients in the main stratum (135 per trial group) who completed the week 36 visit, the geometric mean percentage change in the urinary protein-to-creatinine ratio relative to baseline was significantly greater with atrasentan (-38.1%) than with placebo (-3.1%), with a geometric mean between-group difference of -36.1 percentage points (95% confidence interval, -44.6 to -26.4; P<0.001). The percentage of patients with adverse events did not differ substantially between the two groups. Fluid retention was reported by 19 of 169 patients (11.2%) in the atrasentan group and in 14 of 170 (8.2%) in the placebo group but did not lead to discontinuation of the trial regimen. No apparent cases of cardiac failure or severe edema occurred. In this prespecified interim analysis, atrasentan resulted in a significant and clinically meaningful reduction in proteinuria as compared with placebo in patients with IgA nephropathy. (Funded by Novartis; ALIGN ClinicalTrials.gov number, NCT04573478.).

Perbedaan Perubahan Tekanan Darah Antara yang Diberikan Jus Mentimun (Cucumis Sativus Linn) dengan Jus Pepaya (Carica Papaya) Terhadap Penderita Hipertensi Primer di Wilayah Kerja Puskesmas Ampenan

Hypertension is the leading cause of death in Indonesia and has a high risk of heart failure, stroke, kidney failure and myocardial infarction. Management of hypertension includes lifestyle changes, diet, stress management and others. In addition, giving cucumber juice and papaya juice is also recommended as a nursing management to lower blood pressure because the content of potassium, magnesium, phosphorus can treat hypertension. The purpose of this study was to determine the difference in blood pressure changes between those given cucumber juice (cucumis sativus linn) and papaya juice (carica papaya) for patients with primary hypertension in the Ampenan Health Center work area. The research method used was a Quasy Experimental study with a pretest-posttest control group design with a quantitative approach in the cucumber juice group and the papaya juice group with a control group without treatment. Random sampling technique was used to obtain 30 respondents divided into 3 groups. The results of the study showed that the results of the dependent t test showed a p value = &lt;0.05 so that there was a difference in blood pressure reduction between those given cucumber juice and those given papaya juice in patients with hypertension.

Legacy persistent organic pollutants among multiple cetacean species in the Northwest Atlantic

The historical contamination of eastern Canadian shelf waters remains an ongoing concern, predominantly stemming from anthropogenic discharges in the Great Lakes region. Although legacy persistent organic pollutants (POPs) were banned decades ago, it remains unclear whether their concentrations have sufficiently decreased to safer levels in cetaceans that feed in the continental shelf waters of the northwestern Atlantic. This study compares polychlorinated biphenyl (PCB) and organochlorine pesticide (OC) accumulation in six cetacean species sampled in the Northwest Atlantic from 2015 to 2022. We assessed the influence of relative trophic level and foraging habitat preferences on POP accumulations among species using stable isotopes and fatty acids as dietary tracers. We further identified the species most susceptible to the effects of these contaminants. Killer whales (Orcinus orca) exhibited the highest PCB (∼100 mg/kg lw) and OC concentrations, followed by other odontocetes, with lowest concentrations in mysticetes. Stable isotope analysis revealed an unexpected lack of correlation between δ15N values and contaminant levels. However, there was a positive correlation between δ13C values and POP concentrations. Cetaceans foraging on pelagic prey species, as indicated by elevated proportions of the FA markers 22:1n11 and 20:1n9, had lower contaminant loads compared to cetaceans with benthic/coastal FA signatures. PCB and DDT (dichlorodiphenyltrichloroethane) concentrations are lower now in most cetacean species than in the 1980s and 1990s, likely due to regulatory measures restricting their production and use. Although current PCB concentrations for most species are under the thresholds for high risks of immune and reproductive failure, concentrations in killer whales exceed all established toxicity thresholds, underscoring the need for further action to reduce sources of these contaminants to the continental shelf waters of the northwestern Atlantic.

Optimizing transplanting densities for lowland rice production under low-yielding environments in the Madagascar highlands

ContextRice yield is low at 2.1 t ha−1 in sub-Saharan Africa. Increased yield is a critical challenge to food security and environmental conservation in this region. However, smallholder farmers have limited access to irrigation, mineral fertilizers, and improved crop varieties. One approach that even resource-limited farmers can easily manipulate is to optimize planting densities. However, there is limited empirical evidence to provide technical recommendations under such low-yielding conditions. ObjectiveThis study aimed to identify the effect of dense transplanting on lowland rice yields under low-yielding conditions, with a target range below 5 t ha−1. MethodsMulti-field trials were implemented with transplanting densities of a regular rate at 25–26.7 hills m−2, a doubled rate at 50–53.3 hills m−2, and a tripled rate at 88.9 hills m−2 in the central highlands of Madagascar, where rice yields are limited by nutrient deficiency and low temperature. Canopy coverage and cumulative intercepted radiation (CIR) were monitored from transplantation to maturity using digital imagery analysis. Field observations (n=306) and four-year household surveys (n=356) were combined to calculate the costs and benefits of changing transplanting densities. ResultsDoubling densities from 25.0–26.7 hills m−2 to 50.0–53.3 hills m−2 had a consistent yield advantage by approximately 0.4 t ha−1 across a yield range of 1.8 t ha−1–4.4 t ha−1. The yield was further increased by tripling the transplanting densities to 88.9 hills m−2 when the yield range was 1.9–2.3 t ha−1. The yield advantage of higher transplanting densities was attributed to a greater CIR at the initial growth stages and a significantly greater panicle number. Household surveys and field observations indicated that the benefit of yield gain was more than three times greater than the additional cost of doubling the seed amounts. No significant yield differences were observed by changing the transplanting densities when the yield level was higher than 5 t ha−1 or lower than 1.3 t ha−1 where substantial reductions in grain fertility occurred owing to low-temperature stress. ConclusionsA relatively high transplanting density of 50–53.3 hills m−2 or even higher is recommended to ensure initial canopy development and panicle number in low-yielding conditions where individual plant growth is stagnant, except in fields with high risks of grain set failure. ImplicationsThis study provides an easy-to-use opportunity for smallholder farmers to increase their rice yield. Further studies are required to determine whether these findings apply to warmer climatic conditions.

EndoArt®: results in patients with glaucoma drainage devices

EndoArt® (Eye Yon Medical, Ness Ziona, Israel) is anovel artificial corneal inner layer transplant and an innovative treatment alternative for patients at high risk for graft failure after posterior lamellar corneal transplantation (EK). We present the initial results of the EndoArt® implantation in patients with glaucoma drainage devices (GDD). In this study 12eyes with GDD were retrospectively evaluated. All had ahigh risk of transplant rejection in cases of EK (previous other glaucoma surgery in addition to GDD, n = 8, condition following Descemet membrane endothelial keratoplasty, DMEK, n = 9, uveitis, n = 2, or synechiae, n = 2). The EndoArt® was secured with agas bubble and one to three holding sutures. The preoperative and postoperative best spectacle-corrected visual acuity (BSCVA) and central corneal thickness (CCT) were determined. The need for additional gas injections (rebubbling) was analyzed. Octafluoropropane (C3F8) 12% was used in nine patients and sulfur hexafluoride (SF6) 20% in three patients as anterior chamber tamponade to ensure adhesion of the EndoArt®. At least one rebubbling was necessary in four eyes. The preoperative BSCVA was 1.6 (± 0.5) logMAR and significantly improved to 1.1 (± 0.6) logMAR after 12weeks (p = 0.028). The preoperative CCT was 719 µm ± 145.7, which significantly decreased to 622.4 µm ± 174.9 after six weeks (p = 0.004) and to 591.7 µm ± 190.8 after 12weeks (p = 0.096). In one eye, the prosthesis was explanted due to a suspected fibrotic remodelling of the cornea following multiple previous DMEKs. EndoArt® led to asignificant improvement in BSCVA and reduction in CCT; however, there was ahigh rebubbling rate in patients with GDD. In high-risk patients, the use of EndoArt® may be advantageous in avoiding graft failure after EK.

Patterns of Failure After Definitive Trimodality Therapy for Muscle-Invasive Bladder Cancer

BackgroundReal-world outcomes, especially patterns of failure, are limited for patients with muscle-invasive bladder cancer (MIBC) treated with trimodality therapy (TMT). We aim to evaluate patterns of failure after TMT for MIBC in a typical heterogeneous population. MethodsIn the national Veterans Affairs database, patients with urothelial histology, MIBC (T2-4a/N0-3/M0) who underwent definitive intent TMT between 2000-2018. Successful TMT was defined as ≥ 50% definitive radiation dose and ≥ 1 cycle chemotherapy. Endpoints of any recurrence, metastatic (nonbladder) recurrence (MR), and local (bladder) recurrence (LR) evaluated in multivariable Fine-Gray models. Times to recurrence calculated from radiation start date. ResultsIn 347 patients with MIBC treated with TMT, 65% of patients were deemed ineligible for surgery while 35% were surgically eligible but elected for TMT. Median follow-up time was 77 months. Median overall survival was 32.4 months (95% CI: 28.2-36.7). 154 (44%) patients had no recurrence. 130 (37%) patients developed MR, median time 9.9 months. 117 (34%) patients developed LR, median time 8.7 months. In multivariable models, lymph node positive (LN+) disease (HR:3.31, 95% CI: 1.45-7.55, P < .01) and pretreatment hydronephrosis (HR:1.62, 95% CI:1.11-2.36, P = .01) were associated with higher rates of MR. No patient, tumor, or treatment variables were associated with LR. ConclusionsAcross a multi-institutional and heterogeneous population, TMT is an effective treatment for many real-world patients with MIBC. However, a notable proportion of patients develop MR and/or LR which emphasizes the need for post-treatment surveillance and improved treatment pathways. Identified high risk features (LN+ disease, pretreatment hydronephrosis) and other markers should be further investigated to delineate the patients at high risk of TMT failure who therefore may potentially benefit from augmented treatment, such as additional systemic therapy.

Technology Focus: Sand Management (October 2024)

With the resurgence of drilling activities post-COVID-19, there is a growing interest in refining existing technologies and exploring new ones to discover cost-effective and reliable solutions for developing aged and more-challenging new reservoirs. Although approaches may vary slightly depending on the unique characteristics of reservoirs in different regions, the general trends are conceptually similar. Drilling longer wells, increasing the number of fracture stages, and completing multiple zones in complex stacked reservoirs, along with optimizing multilateral wells with sand control to enable long laterals in stacked reservoirs, have emerged as key focuses of the industry. Drilling longer wells introduces several challenges, including managing installation loads, ensuring proper wellbore cleanout, and ultimately producing effectively and uniformly from extended laterals that drill through heterogeneous reservoirs with varying sand facies. While liner flotation is effective in reducing installation loads and improving wellbore cleaning, it presents challenges when used in conjunction with conventional sand-control screens. Sand control and flow control are becoming more integrated to offer solutions for effective production from longer laterals. Flow segmentation helps prevent premature failures caused by gas or water breakthroughs or localized high rates causing erosion. Paper SPE 218074 is a good example of using flow-control devices to enhance the reliability and longevity of sand-control systems. Stacked reservoirs have always posed challenges in terms of zonal isolation and sand-control design. Higher fines content and silty sand with complex reservoir conditions leads to less interest in standalone screens because of the high risk of plugging and failure in such developments. Even though gravel packing is effective, it poses several technical and implementation challenges. The complexity of sandface completion, with varying sand sizes, pressures, and fluid properties, makes these wells particularly difficult to complete. Paper SPE 214914 offers a good case study of such a complex completion successfully implemented in the field. Despite all this, the fundamentals of screen design and implementation remain the same. Screen plugging remains one of the major challenges in the sand-control industry. Rigorous testing of sand-control media to verify retention properties, erosional resistance, integrity requirements for the installation-loading and lifelong-loading scenarios, and plugging resistance are critical aspects of any sand-control qualification. I strongly recommend reading paper IPTC 23690 for a detailed understanding of the screen-qualification process and the design of screens for target sand facies. Also, it is crucial to remember that no screen is completely immune to plugging. The unintended consequences of a change in drilling/completion fluid or cleanout process could lead to screen plugging. It is always important to test and validate the effect of any change in fluids or completion practices on sand-control performance. Recommended additional reading at OnePetro: www.onepetro.org. SPE 215070 A Comprehensive Review of Screen Plugging During Openhole Sand-Control Completions Installation: Causes, Consequences, and Best Practices by Maye Beldongar, SLB, et al. SPE 214934 Shunted Gravel-Pack Failures and How To Prevent Them by Carolina Latini, DuneFront, et al. SPE 215411 Performance of Bonded Bead Sand Screen as Remedial Sand Control in Highly Erosive Environment by Ashvin Avalani Chandrakant, Petronas, et al.

Defining the complex needs of families with rare diseases-the example of telomere biology disorders.

Families with rare diseases, such as telomere biology disorders (TBDs), may have extensive unmet needs given the heterogeneity, chronicity, and potential severity of illness. TBDs are rare inherited syndromes associated with high risk of bone marrow failure, cancer, pulmonary fibrosis, and other severe, chronic complications. To identify gaps in clinical care, we aimed to ascertain the perceived unmet needs of adults and family caregivers, current or bereaved, of individuals with TBDs. Participants were aged ≥18 years with a self-reported TBD diagnosis and/or ever caregivers to one or more family members with a TBD. Participants completed an online survey (N = 35) and/or an audio-recorded telephone interview (N = 32). We calculated descriptive statistics in SPSS and thematically analyzed interview transcripts. Quantitative and qualitative data were analyzed concurrently. Most participants were aged ≥35 years, female, highly educated, and medically insured. Survey respondents reported numerous unmet needs in psychosocial, medical, financial, and daily activity domains. In interviews, participant descriptions validated and contextualized the salience of these unmet needs. Both qualitative and quantitative data identified critical shortfalls in addressing chronic family distress and specialty care coordination. Adults and caregivers of individuals with TBDs have a high risk of adverse psychosocial sequelae given extensive unmet needs. These findings provide a foundation for understanding the range and extent of gaps in care for families with rare diseases, especially TBDs but that are likely applicable to others. Tailored multi-disciplinary interventions involving patients, families, clinicians, researchers, and patient advocacy communities are required to appropriately address care needs for all rare diseases.

Zn/Cu Bi‐Single‐Atom Nanoplatform: Hexagonal Anti‐Tumor Warrior by ROS Amplification for DOX Resistance Reversal and Immune Activation

AbstractSevere resistance of doxorubicin (DOX) caused by drug efflux and immunosuppression has led to a high treatment failure risk of breast cancer (BC). Compared with the single atom nanozymes, the bi‐single‐atomic nanozymes obtained through sequential single‐atom synthesis strategy in different spaces of the same nanomaterial, can significantly improve the space utilization efficiency and catalytic capacity. In this study, bi‐single‐atom nanozymes (Zn/Cu‐BSAN‐DOX NPs) are designed to reverse BC DOX resistance by causing damage to mitochondria of mesenchymal stem cells (MSCs) and 4T1 cells through reactive oxygen species (ROS) amplification. In situ H2O2 self‐supply is improved by releasing DOX through activating the nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (NOXs). ROS amplification is triggered by enhanced chemodynamic therapy (CDT) and sonodynamic therapy (SDT) of Zn/Cu‐BSAN, which efficiently reverses the DOX resistance by breaking the hyaluronic acid (HA) barrier and DOX efflux. Furthermore, ROS amplification significantly promotes the immune improvement including DCs maturation, T cell activation, and the polarization of M1 macrophage. In summary, as “hexagonal” anti‐tumor warrior, Zn/Cu‐BSAN‐DOX NPs show great potential for multimodal DOX‐resistant BC therapy, which further expands the new preparation strategy and the clinical anti‐tumor application paradigm of single‐atom nanozymes.

Implementation of Waterfall Model and User-Centered Design Integration

User-Centered Design (UCD) is a crucial approach in software development to ensure that the resulting product is user-friendly. However, the implementation of UCD within the software development lifecycle is still rarely discussed. This study aims to examine whether UCD can be integrated into the Waterfall model through the development of a web-based application. The integration process involves applying UCD during the requirements identification phase, followed by the other phases such as analysis, design, implementation, testing, and deployment. The research methods used include observation and interviews with the project implementers of the application development. The findings indicate that integrating UCD into the Waterfall model presents certain challenges, particularly due to the high risk of failure when the development phases do not allow returning to the initial phase that includes the UCD process. The interface evaluation conducted within the UCD process is proven to be crucial for the project's success.

Pseudochamber-Protected Keratoplasty (PPK) with a New Inter-Corneal Surgical Device Implant Technique in High-Risk Cases.

Background/Objectives: To describe the pseudochamber-protected keratoplasty (PPK) procedure with the new Endo-K Pro® implant technique and report the clinical outcomes in patients at high risk for penetrating keratoplasty (PKP). Methods: This case series study included patients who required a PKP and had a high risk for corneal transplant failure. All cases underwent the PPK procedure with simultaneous Endo-K Pro® implantation and had a minimum follow-up of 12 months. Graft survival was the primary outcome (defined as a clear graft with an endothelial cell density >500 cells/mm2). Central corneal thickness (CCT), corrected distance visual acuity (CDVA), intraocular pressure (IOP), and complication rate were the secondary outcomes. Results: Twenty-five eyes (twenty-five patients) were included. The mean follow-up was 23.64 ± 8.2 months (range: 12-36 months). Graft survival was achieved in 23 of the 25 cases (92%). One eye had to be re-transplanted due to persistent oedema secondary to uncontrolled IOP. In two cases (8%), the graft failed three months after surgery when an anterior pseudochamber collapsed due to direct contact of donor endothelium and host tissue. Six eyes experienced host tissue protrusion that was successfully managed using an Nd: YAG laser (two eyes) or injecting a cohesive viscoelastic into the pseudochamber (four eyes). CDVA increased significantly during the follow-up period. No significant changes were found in IOP. No intra- or postoperative complications were reported. Conclusions: PPK with the Endo-K Pro® implant seems to be an effective and safe surgical approach as an alternative in high-risk patients for PKP, allowing full-thickness corneal transplantation without performing an open-sky procedure.