Achievement of Target Gain Larger than Unity in an Inertial Fusion Experiment.

On December 5, 2022, an indirect drive fusion implosion on the National Ignition Facility (NIF) achieved a target gain G_{target} of 1.5. This is the first laboratory demonstration of exceeding "scientific breakeven" (or G_{target}>1) where 2.05 MJ of 351 nm laser light produced 3.1 MJ of total fusion yield, a result which significantly exceeds the Lawson criterion for fusion ignition as reported in a previous NIF implosion [H. Abu-Shawareb et al. (Indirect Drive ICF Collaboration), Phys. Rev. Lett. 129, 075001 (2022)PRLTAO0031-900710.1103/PhysRevLett.129.075001]. This achievement is the culmination of more than five decades of research and gives proof that laboratory fusion, based on fundamental physics principles, is possible. This Letter reports on the target, laser, design, and experimental advancements that led to this result.

Comparative Evaluation of Microleakage of Various Restorative Materials in Pulpotomized Primary Molars - In Vitro Study.

Background and Objectives: Conventionally, stainless steel crown (SSC) is the preferred material for the restoration of pulpotomized primary molars. However, in situations where stainless steel cannot be used necessity for other restorative material arises. Aim: The aim of this study is to assess the microleakage of several coronal seal materials in pulpotomized primary molars- in vitro. Methodology: Seventy-five primary molars were prepared with proximo-occlusal cavities. Restoration was done with Zinc oxide eugenol cement, SSC, composite resin, resin-modified glass-ionomer cement (GIC), and amalgam. Microleakage was assessed using dye penetration technique with stereomicroscope and scanning electron microscope. Statistical Analysis and Results: The Kruskal-Wallis and Mann-Whitney tests were used to statistically analyze the results. Conclusion: With regard to this present study composite resin and resin-modified GIC offers a good alternative for SSC.

Lawson Criterion for Ignition Exceeded in an Inertial Fusion Experiment.

For more than half a century, researchers around the world have been engaged in attempts to achieve fusion ignition as a proof of principle of various fusion concepts. Following the Lawson criterion, an ignited plasma is one where the fusion heating power is high enough to overcome all the physical processes that cool the fusion plasma, creating a positive thermodynamic feedback loop with rapidly increasing temperature. In inertially confined fusion, ignition is a state where the fusion plasma can begin "burn propagation" into surrounding cold fuel, enabling the possibility of high energy gain. While "scientific breakeven" (i.e., unity target gain) has not yet been achieved (here target gain is 0.72, 1.37 MJ of fusion for 1.92 MJ of laser energy), this Letter reports the first controlled fusion experiment, using laser indirect drive, on the National Ignition Facility to produce capsule gain (here 5.8) and reach ignition by nine different formulations of the Lawson criterion.

Dysbiosis and Restoration Dynamics of the Gut Microbiome Following Therapeutic Exposure to Florfenicol in Snubnose Pompano (Trachinotus blochii) to Aid in Sustainable Aquaculture Production Strategies.

Information on unintended effects of therapeutic exposure of antibiotics on the fish gut microbiome is a vital prerequisite for ensuring fish and environmental health during sustainable aquaculture production strategies. The present study forms the first report on the impact of florfenicol (FFC), a recommended antibiotic for aquaculture, on the gut microbiome of snubnose pompano (Trachinotus blochii), a high-value marine aquaculture candidate. Both culture-dependent and independent techniques were applied to identify the possible dysbiosis and restoration dynamics, pointing out the probable risks to the host and environment health. The results revealed the critical transient dysbiotic events in the taxonomic and functional metagenomic profiles and significant reductions in the bacterial load and diversity measures. More importantly, there was a complete restoration of gut microbiome density, diversity, functional metagenomic profiles, and taxonomic composition (up to class level) within 10-15 days of antibiotic withdrawal, establishing the required period for applying proper management measures to ensure animal and environment health, following FFC treatment. The observed transient increase in the relative abundance of opportunistic pathogens suggested the need to apply proper stress management measures and probiotics during the period. Simultaneously, the results demonstrated the inhibitory potential of FFC against marine pathogens (vibrios) and ampicillin-resistant microbes. The study pointed out the possible microbial signatures of stress in fish and possible probiotic microbes (Serratia sp., Methanobrevibacter sp., Acinetobacter sp., and Bacillus sp.) that can be explored to design fish health improvisation strategies. Strikingly, the therapeutic exposure of FFC neither caused any irreversible increase in antibiotic resistance nor promoted the FFC resistant microbes in the gut. The significant transient increase in the numbers of kanamycin-resistant bacteria and abundance of two multidrug resistance encoding genes (K03327 and K03585) in the treated fish gut during the initial 10 days post-withdrawal suggested the need for implementing proper aquaculture effluent processing measures during the period, thus, helps to reduce the spillover of antibiotic-resistant microbes from the gut of the treated fish to the environment. In brief, the paper generates interesting and first-hand insights on the implications of FFC treatment in the gut microbiome of a marine aquaculture candidate targeting its safe and efficient application in unavoidable circumstances. Implementation of mitigation strategies against the identified risks during the initial 15 days of withdrawal period is warranted to ensure cleaner and sustainable aquaculture production from aquatic animal and ecosystem health perspectives.

Characterization of novel L-asparaginases having clinically safe profiles from bacteria inhabiting the hemolymph of the crab, Scylla serrata (Forskål, 1775).

L-asparaginase (ASNase) is the principal chemotherapeutic agent against different blood cancers. The risks associated with current clinical preparations demand screening for novel ASNases. Accordingly, the study was conducted to shortlist ASNases having clinically safer profiles from a novel niche, namely, microbes in the gut and hemolymph of apparently healthy Scylla serrata. A four-step strategic approach incorporating the essential requirements for clinically safer profiles was followed. The initial step through plate assay showed five (9.61%) potential ASNase producers. The relative prevalence of ASNase producers was higher in hemolymph (13.33%) than gut (4.5%). The positive isolates were identified as Priestia aryabhattai, Priestia megaterium, Bacillus altitudinis, Shewanella decolorationis, and Chryseomicrobium amylolyticum. Quantitative profiles revealed high ASNase production (114.29 to 287.36 U/mL) without any optimization, with an added advantage of the extracellular production. The second step for substrate specificity studies revealed the absence of L-glutaminase and urease activities in ASNases from C. amylolyticum and P. megaterium, the most desirable properties for safe clinical applications. This is the first report of glutaminase and urease-free ASNase from these two bacteria. The third step ensured type II nature of selected ASNases, the targeted form in clinical applications. The fourth step confirmed the activity and stability in human physiological conditions. Altogether, the results revealed two potential ASNases with clinically compatible profiles.

Effect of Tricalcium Phosphate and Calcium Sucrose Phosphate on the Inhibition of Streptococcus mutans: An In Vivo Study.

AIM: To determine the efficacy of tricalcium phosphate (TCP) and calcium sucrose phosphate (CSP) on the inhibition of Streptococcus mutans (SM). MATERIALS AND METHODS: Thirty healthy children between 13 and 18 years of age were divided into two groups of 15 each; Group I receiving TCP-containing cream and Group II receiving calcium sucrose phosphate-containing cream. On the first day of the study, 30 minutes after breakfast, baseline plaque samples were taken from the buccal surface of first mandibular permanent molar using a sterile wedge which was immediately transferred to sterile container containing 1 mL of saline, and were subjected to microbiological examination. On the following days, both the creams were applied to the respective groups. On the 16th day, plaque samples were collected from the same site, and colony forming units were recorded using agar plate as a culture medium. RESULTS: The mean of S. mutans count before application of TCP-containing paste was 16.27 cfu per mL and before calcium sucrose phosphate-containing paste was 15.33 cfu per mL. The mean after application of TCP-containing paste and calcium sucrose phosphate-containing paste was 3.53 and 9.87 cfu per mL, respectively. And, there was a statistically significant difference found within the groups. CONCLUSION: Both TCP and CSP have an inhibitory effect on S. mutans. CLINICAL SIGNIFICANCE: This can be an effective preventive tool for children with high caries risk and even for special child. Both TCP and CSP deposit the mineral reservoir in plaque and saliva; it may help resist the future cariogenic challenges.

Analytical validation of a modified turbidimetric assay to screen sulphur oxidizing bacteria.

Conventional turbidimetric assay for sulphate determination was modified to 100 times lesser reaction volume on a convenient format using microtitre plate based platform, targeting routine microbiological applications to screen sulphur oxidizing bacteria (SOB) cultures. The modified assay was linear up to 1500 mg/L of sulphate concentration, which is about 37.5 times more than that of conventional assay. Upon regression analysis, linear equation y = 1.243× + 0.011 was obtained having R2 value of 0.998. The modified assay was fully validated in terms of precision, limit of detection (LOD), limit of quantification (LOQ), sensitivity, selectivity and robustness to assure the reliability during final applications. LOD and LOQ were found as 7.4 mg/L and 24.8 mg/L of sulphate concentration respectively. Further, accuracy of the assay over routine SOB screening media components was tested, and proved as reliable and suitable for the intended application.

Epizootics of epizootic ulcerative syndrome among estuarine fishes of Kerala, India, under post-flood conditions.

Epizootic ulcerative syndrome (EUS), primarily caused by the water mold Aphanomyces invadans, is an OIE-notifiable disease, having potential impacts on fisheries. We report EUS epizootics among estuarine fishes of Kerala, India, during 2018, under post-flood conditions 3 decades after its primary outbreak. Six fish species (Mugil cephalus, Platycephalus sp., Scatophagus argus, Arius sp., Planiliza macrolepis and Epinephelus malabaricus) were infected, including the first confirmed natural case in E. malabaricus and P. macrolepis. Salinity, surface temperature, dissolved oxygen and pH of resident water during the epizootic were <2 ppt, 25°C, 4.1 ppm and 7.0. The presence of zoonotic bacterial pathogens (Aeromonas veronii, Shewanella putrefaciens, Vibrio vulnificus and V. parahaemolyticus) in tissues of affected fish indicates that EUS-infected fish may pose a public health hazard if not handled properly. Lack of clinical evidence in the region during the last 3 decades, a high number of affected fishes, including 2 new fish species, the severity of skin lesions and very low water salinity (<2 ppt) during the outbreak in contrast to historical water salinity records suggest relatively recent invasion by A. invadans. Phylogenetic analysis based on the internal transcribed spacer region of the rRNA gene showed that the same clone of pathogen has spread across different continents regardless of fish species and ecotypes (fresh/estuarine environments). Altogether, the present study provides baseline data which can be applied in EUS management strategies within brackish-water ecosystems. We recommend strict surveillance and development of sound biosecurity measures against the disease.

Coronary artery calcification is inversely related to body morphology in patients with significant coronary artery disease: a three-dimensional intravascular ultrasound study.

AIMS: Emerging data have indicated unexpected complexity in the regulation of vascular and bone calcification. In particular, several recent studies have challenged the concept of a universally positive relationship between body morphology [weight, height, body mass index (BMI), body surface area (BSA)] and the extent of vascular calcification. We sought to clarify these discrepancies and investigated the relationship between index lesion coronary artery calcification (CAC) and body morphology in patients undergoing percutaneous coronary intervention (PCI) using three-dimensional intravascular ultrasound (IVUS). METHODS AND RESULTS: We analysed CAC in patients who underwent PCI with pre-intervention IVUS imaging. The main outcome measure was the calcium index (CalcIndex); a three-dimensional IVUS-derived measure of total calcification per obstructive coronary lesion. A total of 346 patients (65.3 ± 10.6 years; 29.5% females) underwent PCI with IVUS-based CAC assessment. CalcIndex was categorized as zero-low (0-0.1399; n = 152) or intermediate-high (0.1400-1.2541; n = 194). All measures of body morphology were lower in patients with intermediate-high CalcIndex (height, P = 0.024; weight, P = 0.008; BMI, P = 0.064; BSA, P = 0.005). In adjusted multivariable models, weight and BSA were independent inverse predictors of intermediate-high CalcIndex [weight: odds ratio (OR) 0.986, P = 0.017; BSA: OR 0.323, P = 0.012] while CalcIndex also trended towards an inverse association with both height (P = 0.068) and BMI (P = 0.064). These independent inverse associations were consistent across multiple clinical subgroups, including stratification by age, race, gender, diabetes, and renal impairment. CONCLUSION: Using three-dimensional IVUS to assess vascular calcification, these data confirm an independent, inverse relationship between body size and index lesion CAC in patients with obstructive coronary artery disease.

High platelet reactivity on clopidogrel therapy correlates with increased coronary atherosclerosis and calcification: a volumetric intravascular ultrasound study.

OBJECTIVES: This study sought to evaluate the relationship between platelet reactivity and atherosclerotic burden in patients undergoing percutaneous coronary intervention (PCI) with pre-intervention volumetric intravascular ultrasound (IVUS) imaging. BACKGROUND: Atherosclerosis progresses by the pathologic sequence of subclinical plaque rupture, thrombosis, and healing. In this setting, increased platelet reactivity may lead to more extensive arterial thrombosis at the time of plaque rupture, leading to a more rapid progression of the disease. Alternatively, abnormal vessel wall biology with advanced atherosclerosis is known to enhance platelet reactivity. Therefore, it is possible that by either mechanism, increased platelet reactivity may be associated with greater atherosclerotic burden. METHODS: This study included patients who underwent PCI with pre-intervention IVUS imaging and platelet reactivity functional assay (P2Y(12) reaction units) performed >16 h after PCI, after the stabilization of clopidogrel therapy (administered before PCI). Platelet reactivity >230 P2Y(12) reaction units defined high on-treatment platelet reactivity (HPR). RESULTS: Among 335 patients (mean age 65.0 years, 71% men), there were 109 patients with HPR (32.5%) and 226 without HPR (67.5%), with HPR being associated with diabetes and chronic renal insufficiency. By IVUS analysis, patients with HPR had significantly greater target lesion calcium lengths, calcium arcs, and calcium indexes. Furthermore, patients with HPR tended to have longer lesions and greater volumetric dimensions, indicating higher plaque volume, larger total vessel volume, and also greater luminal volume, despite similar plaque burden. By multivariate analysis controlling for baseline clinical variables, HPR was the single consistent predictor of all IVUS parameters examined, including plaque volume, calcium length, and calcium arc. CONCLUSIONS: Increased platelet reactivity on clopidogrel treatment, defined as >230 P2Y(12) reaction units, is associated with greater coronary artery atherosclerotic disease burden and plaque calcification.

Outcome of renal insufficiency patients undergoing coronary artery bypass graft surgery.

Renal insufficiency (RI) is a prognostic marker in patients with cardiovascular disease. In this study, the latest standard of glomerular filtration rate (GFR) calculation, that is the modification of diet in renal disease (MDRD) study equation, is used to measure the difference in the outcome of coronary artery bypass graft (CABG) surgery in various GFR groups. Between 2000 and 2005, 1,055 patients underwent CABG surgery and were categorized into 5 groups according to the National Kidney Foundation guidelines: stage 1 = normal renal function; stage 2 = mild RI; stage 3 = moderate RI; stage 4 = severe RI; stage 5 = end-stage renal failure (excluded). Precautions were taken in RI patients to avoid perioperative hypotension, fluid overload and limited cardioplegia; cardiopulmonary bypass time was kept at a minimum by performing an essential number of grafts only. Thirty-day mortality occurred in 5 of 1,052 patients (0.48%) with no statistical difference in stages 1-4. There was increase in bleed requiring reoperation and total complications from stages 1 to 4, but it was not statistically significant. Preoperative renal dysfunction in CABG surgery patients is an important predictor of outcome. Patients undergoing CABG surgery can have acceptable results without significant increase in complications and mortality provided that risk factors are minimized perioperatively.