Hydraulic Fracturing Design Optimization Guidelines for Heterogeneous Reservoir

This paper describes the journey of hydraulic fracturing design solutions and implementation in Khazzan field. More than 100 wells have been stimulated with hydraulic fracturing in the field in the last decade. Most of these wells were treated with a single-stage massive propped hydraulic fracturing treatment aimed at stimulating the entire vertical productive zone in a single treatment. More recently, hydraulic fracturing has begun on the southern acreage from Khazzan, referred to as Ghazeer. Producing layers in this area are thicker and higher permeability and, as a result, more prolific. Based on the available data and experiences, the establishment of clear guidelines has become a requirement to help the understanding and adjust the hydraulic fracturing design for each well to be become a well-specific optimum design. During the stimulation journey, surveillance techniques have been utilized and implemented in the Khazzan and Ghazeer fields to provide and develop better understanding of the fracture propagation process. These data have proven essential to support stimulation design evolvement and determine if multiple fracturing stages are justified or whether a single stage would be sufficient. Based on a wide range of hydraulic fracture stimulation operations performed across the Khazzan and Ghazeer fields, a flowchart was developed to integrate all the lessons learned from the previous experience and help optimize future fracture design. Clear guidelines include the rationale between the selection of single or multiple fracturing stages, the selection of optimal pad fractions, and other associated details of the fracture design. This flowchart has been extensively validated with surveillance and has proven its inherent value in many stimulated wells, with either single or multiple proppant fracturing stages.

Neuromodulation in 2035

Neuromodulation devices are approved in the United States for the treatment of movement disorders, epilepsy, pain, and depression, and are used off-label for other neurologic indications. By 2035, advances in our understanding of neuroanatomical networks and in the mechanism of action of stimulation, coupled with developments in material science, miniaturization, energy storage, and delivery, will expand the use of neuromodulation devices. Neuromodulation approaches are flexible and modifiable. Stimulation can be targeted to a dysfunctional brain focus, region, or network, and can be delivered as a single treatment, continuously, according to a duty cycle, or in response to physiologic changes. Programming can be titrated and modified based on the clinical response or a physiologic biomarker. In addition to keeping pace with clinical and technological developments, neurologists in 2035 will need to navigate complex ethical and economic considerations to ensure access to neuromodulation technology for a rapidly expanding population of patients. This article provides an overview of systems in use today and those that are anticipated and highlights the opportunities and challenges for the future, some of which are technical, but most of which will be addressed by learning about brain networks, and from rapidly growing experience with neuromodulation devices.

Preclinical Acute Toxicity Assessment of a Crude Polysaccharide Isolated from the Stem of Solanum Nigrum: A Preliminary Analysis

The polysaccharide isolated from Solanum nigrum was proven to possess an immunomodulatory effect and able to suppress the progression of tumor cells by proxy. However, data on the toxicity profile is still limited. The present preclinical study was conducted to investigate the toxicity potential of the crude polysaccharide sample. The acute toxicity experimental design was adapted from OECD 423 guideline. Nine female BALB/c mice were randomly divided into 3 groups, 3 mice per group (n=3). Mice in group A (first-step treatment) were orally administered with a single treatment of crude polysaccharide sample at concentration 2,000 mg/kg/bw (300 µL). Mice in group B (second-step treatment) were received the single treatment after 24 hours, depending on the observation of mice in group A. Mice in group C served as control. Mortality and clinical signs associated with toxicity were observed within 24 hours of treatment session and for the subsequence 14 days for delay-death detection. Mice body weight was recorded starting at day-0 until day-14 prior to sacrificing at day-15. Blood, liver, and kidney were harvested for toxicology assessment. Within 24 hours of treatment, 1 mouse in group A was found to died, while no mortality and delay-death were observed in groups B and C. Referring to OECD 423, it was estimated that the LD50 of the treated sample was 2,500–5,000 mg/kg/bw. No significant changes (p<0.05) were detected in terms of body weight and organ weight indexes of the treated mice as compared to control. The polysaccharide treatment also revealed no significant elevation in mice serum glucose levels. The present findings indicated that the treatment of crude polysaccharide sample exerted a very mild acute toxicity effect when orally administered at 2,000 mg/kg/bw, with no delay-death.

Effect of Multimodal Intervention Care on Cachexia in Patients with Advanced Cancer Compared To Conventional Management (MIRACLE): An Open-Label, Parallel, Randomized, Phase 2 Trial

Background: the context and purpose of the studyCancer cachexia (CC) is a multifactorial process characterized by progressive weight loss, muscle mass, and fat tissue wasting, which adversely affects the quality of life and survival of patients with advanced stages of cancer. CC has a complex and multifactorial pathophysiology, and there is no established standard treatment. Therefore, it is often irreversible and a single treatment modality is unlikely to suppress its progression. We are conducting a randomized trial to investigate the efficacy and safety of a multimodal intervention compared to the best supportive care for patients who received palliative chemotherapy.Methods: how the study will be performedPatients with lung or gastrointestinal cancers undergoing palliative chemotherapy are eligible. Patients are randomized into a multimodal intervention care (MIC) arm versus a conventional palliative care (CPC) arm. MIC includes ibuprofen, omega-3-fatty acid, oral nutritional supplement, weekly physical, psychiatric assessment, nutritional counseling, and complementary and alternative medicine. CPC includes basic nutritional counseling and megestrol acetate as needed (i.e., anorexia ≥ grade 2). All interventions are performed for 12 weeks per subject. The co-primary outcomes are median change (kg) in total lean body mass and handgrip strength (kg) from the baseline. A total of 112 patients will be assigned to the two arms (56 in each group). Discussion: a brief summary and potential implicationsThe purpose of this study is to evaluate the effect of MIC in preventing or alleviating CC in patients who underwent palliative chemotherapy. As there is no established single treatment for CC, it is expected that the results of this clinical trial will provide new insights to significantly improve the quality of life of patients with cancer. Considering the complex mechanisms of cachexia, the effect of MIC rather than a single specific drug is more promising. In this study, we did not overly restrict the type of cancer or chemotherapy. Therefore, we attempted to measure the effects of complex interventions while preserving clinical situations. Thus, it is expected that the results of this study can be applied effectively to real-world practice.Trial registration: If your article reports the results of a health care intervention on human participants, it must be registered in an appropriate registry and the registration number and date of registration should be in stated in this section. If it was not registered prospectively (before enrollment of the first participant), you should include the words 'retrospectively registered'. See our editorial policies for more information on trial registration.This clinical trial was registered in the Clinical Research Information Service (KCT0004967), Korean Clinical Trial Registry on April 27, 2020, and ClinicalTrial.gov (NCT 04907864) on June 1, 2021.

Sequential Hydrothermal HCl Pretreatment and Enzymatic Hydrolysis of Saccharina japonica Biomass

This study investigated the production of fermentable sugars from carbohydrate-rich macroalgae Saccharina japonica using sequential hydrolysis (hydrothermal acid pretreatment and enzymatic hydrolysis) to determine the maximum reducing sugar yield (RSy). The sequential hydrolysis was predicted by three independent variables (temperature, time, and HCl concentration) using response surface methodology (RSM). Enzymatic hydrolysis (8.17% v/wbiomass Celluclast® 1.5 L, 26.4 h, 42.6 °C) was performed after hydrothermal acid pretreatment under predicted conditions (143.6 °C, 22 min, and 0.108 N HCl concentration). Using this experimental procedure, the yields of hydrothermal acid pretreatment, enzymatic hydrolysis, and sequential hydrolysis were 115.6 ± 0.4 mg/g, 117.7 ± 0.3 mg/g, and 183.5 ± 0.6 mg/g, respectively. Our results suggested that sequential hydrolysis of hydrothermal acid pretreatment and enzymatic hydrolysis was more efficient than their single treatment.

Pengaruh Abu Vulkanis Gunung Agung dan Pupuk Kompos terhadap Beberapa Sifat Tanah dan Hasil Kacang Tunggak (Vigna unguiculata (L.) Walp.)

The Effect of the Mount Agung Volcanic Ash and Compost on Soil Properties and Yield of Tunggak Nuts (Vigna unguiculata (L.) Walp). The purpose of this study was to determine the effect of giving volcanic ash and compost as a soil amendment. The design used was a factorial randomized block design. The volcanic ash factor consisted of 3 levels: A0 = no volcanic ash, A1 = 15% volcanic ash and A2 = 30% volcanic ash. The compost factor consisted of 3 levels: K0 = without compost, K1 = 10 tons of compost ha-1, and K2 = 20 tons of compost ha-1. The combination treatments was repeated 3 times so that there were 27 observation units. Several parameters of soil properties and yield of tunggak nuts were studied to determine the effect of volcanic ash and compost as soil amendments. The results showed that the interaction between the treatment of volcanic ash and compost on the soil and plants was not significant, while the single treatment of compost had a significant effect on the growth and yield of tunggak nuts. The treatment of volcanic ash has not shown a significant effect, both on soil and on plant growth and yield.

Treatment of Fistulizing Perianal Crohn’s Disease by Autologous Microfat Enriched With Adipose-Derived Regenerative Cells

In this pilot study, short-term efficacy and safety of fat graft enriched with Adipose-Derived Regenerative Cells (ADRC) in the treatment of Crohn’s high anal fistula was evaluated. Clinical fistula healing was achievable in 75% of cases, by a single treatment.

Treatment of age-related visual impairment with a mitochondrial-acting peptide.

Age-related visual decline and disease due to neural dysfunction are major sources of disability that have resisted effective treatment. In light of evidence that visual impairment and mitochondrial dysfunction advance with age, we characterized age-related decline of spatial visual function in mice and investigated whether treating aged mice with a drug, Elamipretide (SS31), that has been reported to improve mitochondrial function would treat it. Impaired photopic acuity measured with a virtual optokinetic system emerged near 18 months, and declined to ∼40% below normal by 34 months. Daily application of the synthetic peptide Elamipretide, which has high selectivity for mitochondrial membranes that contain cardiolipin, and promotes efficient electron transfer, was able to mitigate visual decline from 18 months. Daily application from 24 months, when acuity was reduced by ∼16%, reversed visual decline and normalized function within 2 months; recovered function that persisted for at least 3 months after treatment was withdrawn. A single treatment at 24 months also delayed subsequent visual decline. Daily application from 32 months took longer to affect change, but enabled substantial improvement within 2 months. The effects of age and Elamipretide treatment on contrast sensitivity were similar to those on acuity, systemic and eye drop applications of Elamipretide had comparable effects, scotopic spatial visual function was largely unaffected by age or treatment, and altered function was independent of variation in optical clarity. These data indicate that Elamipretide treatment adaptively alters the aging visual system, and provide a rationale to investigate whether mitochondrial dysfunction is a treatable pathophysiology of human visual aging and age-related visual disease.