Summary
Background
There has been considerable interest in the possible adverse neurocognitive effects of exposure to general anesthesia and surgery in early childhood.
Aims
The aim of this data ...linkage study was to investigate developmental and school performance outcomes of children undergoing procedures requiring general anesthesia in early childhood.
Methods
We included children born in New South Wales, Australia of 37+ weeks’ gestation without major congenital anomalies or neurodevelopmental disability with either a school entry developmental assessment in 2009, 2012, or Grade‐3 school test results in 2008‐2014. We compared children exposed to general anesthesia aged <48 months to those without any hospitalization. Children with only 1 hospitalization with general anesthesia and no other hospitalization were assessed separately. Outcomes included being classified developmentally high risk at school entry and scoring below national minimum standard in school numeracy and reading tests.
Results
Of 211 978 children included, 82 156 had developmental assessment and 153 025 had school test results, with 12 848 (15.7%) and 25 032 (16.4%) exposed to general anesthesia, respectively. Children exposed to general anesthesia had 17%, 34%, and 23% increased odds of being developmentally high risk (adjusted odds ratio aOR: 1.17; 95% CI: 1.07‐1.29); or scoring below the national minimum standard in numeracy (aOR: 1.34; 95% CI: 1.21‐1.48) and reading (aOR: 1.23; 95% CI: 1.12‐1.36), respectively. Although the risk for being developmentally high risk and poor reading attenuated for children with only 1 hospitalization and exposure to general anesthesia, the association with poor numeracy results remained.
Conclusion
Children exposed to general anesthesia before 4 years have poorer development at school entry and school performance. While the association among children with 1 hospitalization with 1 general anesthesia and no other hospitalization was attenuated, poor numeracy outcome remained. Further investigation of the specific effects of general anesthesia and the impact of the underlying health conditions that prompt the need for surgery or diagnostic procedures is required, particularly among children exposed to long duration of general anesthesia or with repeated hospitalizations.
Tip-enhanced Raman spectroscopy (TERS) is a powerful tool for non-destructive and label-free surface molecular mapping at the nanoscale. However, to date nanoscale resolution chemical imaging in a ...liquid environment has not been possible, in part due to the lack of robust TERS probes that are stable when immersed in a liquid. In this work, we have addressed this challenge by developing plasmonically-active TERS probes with a multilayer metal coating structure that can be successfully used within a liquid environment. Using these novel TERS probes, we have compared the plasmonic enhancement of TERS signals in air and water environments for both gap mode and non-gap mode configurations and show that in both cases the plasmonic enhancement decreases in water. To better understand the signal attenuation in water, we have performed numerical simulations that revealed a negative correlation between the electric field enhancement at the TERS probe-apex and the refractive index of the surrounding medium. Finally, using these robust probes we demonstrate TERS imaging with nanoscale spatial resolution in a water environment for the first time by employing single-wall carbon nanotubes as a model sample. Our findings are expected to broaden the scope of TERS to a range of scientific disciplines in which nanostructured solid-liquid interfaces play a key role.
In this review, we scope the role of interpersonal relationships in students' academic motivation, engagement, and achievement. We argue that achievement motivation theory, current issues, and ...educational practice can be conceptualized in relational terms. Influential theorizing, including attribution theory, expectancy-value theory, goal theory, self-determination theory, self-efficacy theory, and self-worth motivation theory, is reviewed in the context of the role of significant others in young people's academic lives. Implications for educational practice are examined in the light of these theoretical perspectives and their component constructs and mechanisms. A trilevel framework is proposed as an integrative and relationally based response to enhance students' motivation, engagement, and achievement. This framework encompasses student-level action (universal programs and intervention, targeted programs for at-risk populations, extracurricular activity, cooperative learning, and mentoring), teacher- and classroom-level action (connective instruction, professional development, teacher retention, teacher training, and classroom composition), and school-level action (school as community and effective leadership).
The 2019/20 Black Summer bushfire disaster in southeast Australia was unprecedented: the extensive area of forest burnt, the radiative power of the fires, and the extraordinary number of fires that ...developed into extreme pyroconvective events were all unmatched in the historical record. Australia’s hottest and driest year on record, 2019, was characterised by exceptionally dry fuel loads that primed the landscape to burn when exposed to dangerous fire weather and ignition. The combination of climate variability and long-term climate trends generated the climate extremes experienced in 2019, and the compounding effects of two or more modes of climate variability in their fire-promoting phases (as occurred in 2019) has historically increased the chances of large forest fires occurring in southeast Australia. Palaeoclimate evidence also demonstrates that fire-promoting phases of tropical Pacific and Indian ocean variability are now unusually frequent compared with natural variability in pre-industrial times. Indicators of forest fire danger in southeast Australia have already emerged outside of the range of historical experience, suggesting that projections made more than a decade ago that increases in climate-driven fire risk would be detectable by 2020, have indeed eventuated. The multiple climate change contributors to fire risk in southeast Australia, as well as the observed non-linear escalation of fire extent and intensity, raise the likelihood that fire events may continue to rapidly intensify in the future. Improving local and national adaptation measures while also pursuing ambitious global climate change mitigation efforts would provide the best strategy for limiting further increases in fire risk in southeast Australia.
Multiple climate contributors to fire risk in southeast Australia have led to an increase in fire extent and intensity over the past decades that will likely continue into the future, suggests a synthesis of climate variability, long-term trends and palaeoclimatic evidence.
Lutetium-177 177LuLu-PSMA-617 is a radiolabelled small molecule that delivers β radiation to cells expressing prostate-specific membrane antigen (PSMA), with activity and safety in patients with ...metastatic castration-resistant prostate cancer. We aimed to compare 177LuLu-PSMA-617 with cabazitaxel in patients with metastatic castration-resistant prostate cancer.
We did this multicentre, unblinded, randomised phase 2 trial at 11 centres in Australia. We recruited men with metastatic castration-resistant prostate cancer for whom cabazitaxel was considered the next appropriate standard treatment. Participants were required to have adequate renal, haematological, and liver function, and an Eastern Cooperative Oncology Group performance status of 0–2. Previous treatment with androgen receptor-directed therapy was allowed. Men underwent gallium-68 68GaGa-PSMA-11 and 2-flourine-1818Ffluoro-2-deoxy-D-glucose (FDG) PET-CT scans. PET eligibility criteria for the trial were PSMA-positive disease, and no sites of metastatic disease with discordant FDG-positive and PSMA-negative findings. Men were randomly assigned (1:1) to 177LuLu-PSMA-617 (6·0–8·5 GBq intravenously every 6 weeks for up to six cycles) or cabazitaxel (20 mg/m2 intravenously every 3 weeks for up to ten cycles). The primary endpoint was prostate-specific antigen (PSA) response defined by a reduction of at least 50% from baseline. This trial is registered with ClinicalTrials.gov, NCT03392428.
Between Feb 6, 2018, and Sept 3, 2019, we screened 291 men, of whom 200 were eligible on PET imaging. Study treatment was received by 98 (99%) of 99 men randomly assigned to 177LuLu-PSMA-617 versus 85 (84%) of 101 randomly assigned to cabazitaxel. PSA responses were more frequent among men in the 177LuLu-PSMA-617 group than in the cabazitaxel group (65 vs 37 PSA responses; 66% vs 37% by intention to treat; difference 29% (95% CI 16–42; p<0·0001; and 66% vs 44% by treatment received; difference 23% 9–37; p=0·0016). Grade 3–4 adverse events occurred in 32 (33%) of 98 men in the 177LuLu-PSMA-617 group versus 45 (53%) of 85 men in the cabazitaxel group. No deaths were attributed to 177LuLu-PSMA-617.
177LuLu-PSMA-617 compared with cabazitaxel in men with metastatic castration-resistant prostate cancer led to a higher PSA response and fewer grade 3 or 4 adverse events. 177LuLu-PSMA-617 is a new effective class of therapy and a potential alternative to cabazitaxel.
Prostate Cancer Foundation of Australia, Endocyte (a Novartis company), Australian Nuclear Science and Technology Organization, Movember, The Distinguished Gentleman's Ride, It's a Bloke Thing, and CAN4CANCER.
•Presents an in-depth survey of blockchain and its underlying technologies.•Investigates the data privacy requirements and redefines the data privacy concept in blockchain.•Presents a systematic ...survey on the blockchain security threats along with their attack vectors, cause and the proposed countermeasures.•Identifies the critical open challenges that restricts the practicality of blockchain and provides a roadmap of encouraging research avenues for which future research is required.
Blockchain is a distributed, decentralized public ledger that has gained massive momentum recently. Currently, security services such as privacy, confidentiality, resource provenance, access control, authentication and integrity assurance are managed by centralized controllers. However, this centralization faces numerous security and privacy challenges. Blockchain solve such challenges as it helps to create an attack resistant, digital data storage as well as sharing platform by employing linked block structures for data verification and trusted consensus mechanism for data synchronization. The goals of this paper are to provide an in-depth survey of blockchain technology, to provide insights into the blockchain security threats, to highlight the privacy necessities for current applications, to outline their challenges and give an insight on how these challenges can be resolved by the blockchain technology. Furthermore, we summarize the future research challenges associated with the usage of blockchain based security services to spur further investigation in this field.
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To meet the growing demand for food, substantial improvements in yields are needed. This is particularly the case for wheat, where global yield has stagnated in recent years. Increasing ...photosynthesis has been identified as a primary target to achieve yield improvements. To increase leaf photosynthesis in wheat, the level of the Calvin–Benson cycle enzyme sedoheptulose-1,7-biphosphatase (SBPase) has been increased through transformation and expression of a Brachypodium distachyon SBPase gene construct. Transgenic lines with increased SBPase protein levels and activity were grown under greenhouse conditions and showed enhanced leaf photosynthesis and increased total biomass and dry seed yield. This showed the potential of improving yield potential by increasing leaf photosynthesis in a crop species such as wheat. The results are discussed with regard to future strategies for further improvement of photosynthesis in wheat.
This article is part of the themed issue ‘Enhancing photosynthesis in crop plants: targets for improvement’.
DNA replication stress can cause chromosomal instability and tumor progression. One key pathway that counteracts replication stress and promotes faithful DNA replication consists of the Fanconi ...anemia (FA) proteins. However, how these proteins limit replication stress remains largely elusive. Here we show that conflicts between replication and transcription activate the FA pathway. Inhibition of transcription or enzymatic degradation of transcription-associated R-loops (DNA:RNA hybrids) suppresses replication fork arrest and DNA damage occurring in the absence of a functional FA pathway. Furthermore, we show that simple aldehydes, known to cause leukemia in FA-deficient mice, induce DNA:RNA hybrids in FA-depleted cells. Finally, we demonstrate that the molecular mechanism by which the FA pathway limits R-loop accumulation requires FANCM translocase activity. Failure to activate a response to physiologically occurring DNA:RNA hybrids may critically contribute to the heightened cancer predisposition and bone marrow failure of individuals with mutated FA proteins.
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•Replication and transcription collisions cause genome instability in FA•A functional FA pathway protects cells from unscheduled accumulation of R-loops•Transcription inhibition or R-loop removal restores normal replication in FA cells•FANCM resolves R-loops via its translocase activity
Schwab et al. show that the FA pathway prevents DNA lesions caused by conflicts between replication and transcription and by transcription-associated DNA:RNA hybrids (R-loops). FA proteins can stabilize stalled replication forks, and FANCM resolves R-loops via its translocase activity.
There is a challenge for metalloenzymes to acquire their correct metals because some inorganic elements form more stable complexes with proteins than do others. These preferences can be overcome ...provided some metals are more available than others. However, while the total amount of cellular metal can be readily measured, the available levels of each metal have been more difficult to define. Metal-sensing transcriptional regulators are tuned to the intracellular availabilities of their cognate ions. Here we have determined the standard free energy for metal complex formation to which each sensor, in a set of bacterial metal sensors, is attuned: the less competitive the metal, the less favorable the free energy and hence the greater availability to which the cognate allosteric mechanism is tuned. Comparing these free energies with values derived from the metal affinities of a metalloprotein reveals the mechanism of correct metalation exemplified here by a cobalt chelatase for vitamin B
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