Increases in recorded childhood cancer incidence are widely reported, but do not necessarily represent real increases in risk. Time trends might conceal underlying steps caused by changes in ...diagnosis and registration procedures.
Using records from the National Registry of Childhood Tumours 1966-2005 (N=54650), the age-sex-standardised rate for residents of Great Britain aged under 15 years was calculated by individual year of diagnosis for each cancer subtype, and the average annual percentage change (trend) was assessed. The timing of assumed step changes in rate was estimated by iterative Poisson regression, and compared graphically with the approximate timing of innovations previously identified from published sources.
Estimated timing of underlying steps approximately coincided with the following relevant innovations: biochemical assays, mid-1980s (hepatic and germ-cell cancer); diagnostic imaging, mid-1980s to early 1990s (intracranial/intraspinal tumours, neuroblastoma, soft-tissue sarcoma); revised cancer registration scheme, 1971 (leukaemia, bone and soft-tissue sarcoma); mandatory registration, 1993 (intracranial/intraspinal tumours, retinoblastoma, melanoma/carcinoma); cancer registration improvements, 2001 (leukaemia, renal and hepatic cancer).
While the possibility of some real change in risk cannot be excluded, for many cancer subtypes the estimated timing of underlying step changes in rate appeared to correspond with changes in diagnosis or registration procedures. Childhood cancer may have been considerably under-recorded in the past.
Tobramycin is a broad-spectrum aminoglycoside antibiotic agent. The compound is obtained from the base-catalyzed hydrolysis of carbamoyltobramycin (CTB), which is naturally produced by the ...actinomycete Streptoalloteichus tenebrarius. However, the strain uses the same precursors to synthesize several structurally related aminoglycosides. Consequently, the production yields of tobramycin are low, and the compound’s purification is very challenging, costly, and time-consuming. In this study, the production of the main undesired product, apramycin, in the industrial isolate Streptoalloteichus tenebrarius 2444 was decreased by applying the fermentation media M10 and M11, which contained high concentrations of starch and dextrin. Furthermore, the strain was genetically engineered by the inactivation of the aprK gene (∆aprK), resulting in the abolishment of apramycin biosynthesis. In the next step of strain development, an additional copy of the tobramycin biosynthetic gene cluster (BGC) was introduced into the ∆aprK mutant. Fermentation by the engineered strain (∆aprK_1-17L) in M11 medium resulted in a 3- to 4-fold higher production than fermentation by the precursor strain (∆aprK). The phenotypic stability of the mutant without selection pressure was validated. The use of the engineered S. tenebrarius 2444 facilitates a step-saving, efficient, and, thus, more sustainable production of the valuable compound tobramycin on an industrial scale.
The first antibiotic-producing actinomycete (
) was described by Waksman and Woodruff in 1940. This discovery initiated the "actinomycetes era", in which several species were identified and ...demonstrated to be a great source of bioactive compounds. However, the remarkable group of microorganisms and their potential for the production of bioactive agents were only partially exploited. This is caused by the fact that the growth of many actinomycetes cannot be reproduced on artificial media at laboratory conditions. In addition, sequencing, genome mining and bioactivity screening disclosed that numerous biosynthetic gene clusters (BGCs), encoded in actinomycetes genomes are not expressed and thus, the respective potential products remain uncharacterized. Therefore, a lot of effort was put into the development of technologies that facilitate the access to actinomycetes genomes and activation of their biosynthetic pathways. In this review, we mainly focus on molecular tools and methods for genetic engineering of actinomycetes that have emerged in the field in the past five years (2015-2020). In addition, we highlight examples of successful application of the recently developed technologies in genetic engineering of actinomycetes for activation and/or improvement of the biosynthesis of secondary metabolites.
Completeness of ascertainment is a very important aspect of cancer registration. There is no recent published estimate for childhood cancer in Britain.
We estimated completeness of ascertainment by ...the National Registry of Childhood Tumours for cancer diagnosed under age 15 years in residents of Britain during 2003-04. Stratified two-source capture-recapture was applied to notifications from general cancer registries (CRs) and specialist clinicians. Variation in notification patterns was assessed by logistic regression. Results were verified by cross-checking with Hospital Episode Statistics for leukaemia patients from England born in 1998 and diagnosed before 2005.
CRs notified 92-96% of registrations, and specialist clinicians 93%. Notification patterns varied slightly according to registry region, age at diagnosis, diagnostic group, socioeconomic status, and whether the patient had died. Irrespective of stratification by these factors, the overall completeness estimate was 99-100% (assuming independence of sources). Estimated completeness was at least 99% within all subgroups, except for one region (Thames 98-99%) and two small diagnostic groups (germ-cell and gonadal cancer 98-99%, melanoma and non-skin cancer 97-98%).
The independence assumption cannot be fully justified, as both sources used records from treatment centres. With this caveat, ascertainment of recently diagnosed childhood cancer in Britain appears to be virtually complete.
This paper describes the treatment and survival of 1576 children with retinoblastoma in Great Britain diagnosed 1963-2002.
Survival rates were analysed according to period of diagnosis and tumour ...laterality.
Survival was calculated by calendar period of diagnosis, 1963-1982 and 1983-2002. For both unilateral and bilateral retinoblastoma, survival improved between the two periods. The survival curves for the two periods were significantly different: for unilateral retinoblastoma p<0.00001, for bilateral p<0.01. For unilateral cases, the estimated 5-year survival rates rose from 85% for those diagnosed in 1963-1967 to 97% for those diagnosed in 1998-2002. The equivalent rates for bilateral cases were 88% and 100%.
Survival rates were already high at the start of the study period. They increased with changes in treatment regimens.
Summary
It is important to understand parental effects on early life history of fish as manifested, for example, in individual fitness of offspring. Immediately after fertilization, parental ...contributions (both genetic and non‐genetic) to embryos will affect larval ontogeny, physiology, morphology and survival. In marine fish, rates of natural mortality are highest during early life and are negatively correlated with rates of growth and body size. In these early life stages (eggs, larvae, young juveniles) subtle differences in mortality can cause large differences in recruitment and year‐class success. Therefore, it is particularly critical to understand factors that contribute to variability in mortality during early life. This study focuses on evaluating the potential influence of paternity on rates of mortality and development in eggs and larvae of Northwest Atlantic cod, Gadus morhua. To accomplish this 12 males and two females were crossed using a full‐factorial breeding design. Paternity had a strong influence on fertilization success, hatching success, cumulative embryonic mortality, larval standard length, eye diameter, yolk‐sac area, and cumulative larval mortality. Female 1 showed an overall ‘weaker’ performance of offspring than Female 2, indicating that deviances can stem from differences in female quality. Nevertheless, paternal contributions to embryonic and larval development were still evident despite differences in female quality, showing that sire effects on offspring are undeniable and can serve as important sources of variation during early life stages in fishes. Overall, these findings have implications for furthering the understanding of recruitment variability and can be used to optimize reproductive output for the aquaculture industry. In addition, the data suggests that the choice of mate during spawning can play a large role in offspring fitness.
Essentials
The risk for venous thromboembolism after liver surgery remains high in the modern era.
We evaluated the safety/efficacy of extended anticoagulation in liver surgery.
This protocol reports ...zero venous thromboembolism events in 124 liver surgery patients.
Extended anticoagulation after oncologic liver surgery is safe and effective.
Summary
Background
The incidence of venous thromboembolism (VTE) after liver surgery remains high.
Objective
To evaluate the safety and efficacy of extended pharmacologic thromboprophylaxis after liver surgery for the prevention of VTE.
Patient/Methods
From August 2013 to April 2015, 124 patients who underwent liver resection for malignancy were placed on an extended pharmacologic thromboprophylaxis protocol. Intraoperative VTE prophylaxis included thromboembolic deterrent hoses and sequential compression devices. Once hemostasis had been ensured following hepatectomy, daily anticoagulant VTE prophylaxis was initiated for the duration of hospitalization. After hospital discharge, the large majority of patients (114, 91.9%) continued to receive anticoagulant thromboprophylaxis (enoxaparin) to complete a total course of 14 days after minor/minimally invasive hepatectomy or 28 days after major hepatectomy or a history of VTE.
Results
The cohort included 39 (31.2%) major hepatectomies and 38 (31.5%) minor/minimally invasive approaches. The intraoperative, postoperative and overall transfusion rates were 5.6%, 8.1%, and 10.5%, respectively. Pharmacologic thromboprophylaxis was started on postoperative day (POD) 0 for 40 (32.3%) patients and on POD 1 for 84 (67.7%) patients. During 90 days of follow‐up, no postoperative symptomatic deep vein thrombosis or pulmonary embolic events were diagnosed. Standard‐protocol computed tomography scans of the chest, abdomen and pelvis that were obtained for 112 (90.3%) study patients showed no pulmonary emboli, or other thoracic, splanchnic or ileofemoral vein thromboses. Two (1.6%) patients had minor bleeding events that resolved after discontinuation of enoxaparin, requiring neither blood transfusion nor reoperation. The severe complication rate was 5.6%, with no 90‐day mortalities.
Conclusions
These preliminary data suggest that extended pharmacologic thromboprophylaxis for liver surgery patients is safe and effective.
Understanding the impact of order and disorder is of fundamental importance to perceive and to appreciate the functionality of modern photonic metasurfaces. Metasurfaces with disordered and amorphous ...inner arrangements promise to mitigate problems that arise for their counterparts with strictly periodic lattices of elementary unit cells such as, e.g., spatial dispersion, and allows the use of fabrication techniques that are suitable for large scale and cheap fabrication of metasurfaces. In this study, we analytically, numerically and experimentally investigate metasurfaces with different lattice arrangements and uncover the influence of lattice disorder on their electromagnetic properties. The considered metasurfaces are composed of metal-dielectric-metal elements that sustain both electric and magnetic resonances. Emphasis is placed on understanding the effect of the transition of the lattice symmetry from a periodic to an amorphous state and on studying oblique illumination. For this scenario, we develop a powerful analytical model that yields, for the first time, an adequate description of the scattering properties of amorphous metasurfaces, paving the way for their integration into future applications.
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