Complication profiling and Evolution of pelvic exenteration surgery performed in high volume tertiary referral centres over thirty years

Objective: To examine the changes in exenterative surgery over three decades analysing oncological outcomes and whether changes in surgical approach have led to improved patient outcomes Background: Advances in surgical technology, perioperative care and pattern of disease recurrence have coincided with an evolutionary change in exenterative surgery. Methods: A review of prospectively maintained databases of pelvic exenteration surgery from 1988 – 2018 at two high volume specialised institutions. The total cohort was divided into three major time points (1988- 2004, 2005-2010 and 2011 to 2018) to allow comparative analysis. Primary endpoints were overall survival in primary and recurrent disease at each time point. Secondary endpoints included anastomotic leak, blood transfusion, ileus, wound infection rates and evolution of case complexity. Data were analysed using R with a p<0.05 considered significant. Results: Six hundred and seventy patients underwent exenterative surgery. In 2011–2018 there was an increase in resection of recurrent malignancy with a continuous increase in gastro-intestinal malignancies resected over each time period(p<0.001,<0.01) and a reduction in gynaecological malignancy(p<0.001). A significant increase in sacrectomy, pelvic sidewall resection and ileal conduit reconstruction was observed (p<0.01,<0.001). In 2005–2010 patients had increased rates of ileus and anastomotic leak(p<0.05). Patients undergoing resection for primary disease had improved overall survival at time points 1998-2004 and 2011–2018 compared to those with recurrent disease(p=0.007,<0.001). Overall survival was significantly improved in patients with primary versus recurrent disease(p=0.022). Conclusion: There has been a significant improvement in survival in patients undergoing pelvic exenteration surgery from primary disease. Case complexity has increased without significant morbidity. BACKGROUND: The oncological role of pelvic exenteration for locally advanced and recurrent pelvic malignancies arising from the anorectum, gynaecological or urological systems is now well established. Despite this, the surgical community has been slow to accept pelvic exenteration, undoubtedly owing to concerns about high morbidity and mortality rates based on historical data. Therefore, the aims of this study were to assess the general major complications and predictors of morbidity following exenterative surgery for locally advanced and recurrent pelvic malignancies. METHODS: Data were collected from prospective databases at two high-volume institutions specialising in beyond TME surgery for locally advanced and recurrent pelvic malignancies between 1990 and 2015. The primary outcome measures were major complications (Clavien-Dindo 3 or above) and predictors for morbidity. RESULTS: A total of 646 consecutive patients requiring exenterative surgery for local advanced pelvic malignancies were identified. The median age was 63 years (range 19-89 years), and the majority were female patients (371; 57.4%). Five hundred and forty patients did not suffer a major complication (83.6%) following pelvic exenterative surgery. One or more major complications were observed in the remaining 106 patients (16.4%). The most common major complications were intra-abdominal collection (43.7%; n=59/135) and wound infection (14.1%; n=19/135). The overall inpatient mortality rate was 0.46% (n=3/646). Independent predictors for major morbidity following exenterative surgery for locally advanced or recurrent pelvic malignancies were squamous cell carcinoma of anus, sacrectomy, past history of peripheral vascular disease and requirement for blood transfusion. CONCLUSION: Our series adds to the increasing evidence that good outcomes can be achieved for pelvic exenterative surgery in locally advanced and recurrent pelvic malignancies. A coordinated approach in specialist centres for beyond TME surgery demonstrates this is a safe and feasible procedure, offering low major complication rates

Custom Integrated Circuits

Contains reports on nine research projects.Analog Devices, Inc.International Business Machines, Inc.Joint Services Electronics Program (Contract DAALO03-86-K-0002)U.S. Air Force - Office of Scientific Research (Grant AFOSR 86-0164)Rockwell International CorporationOKI SemiconductorU.S. Navy - Office of Naval Research (Contract N00014-81-K-0742)Charles Stark Draper LaboratoryDARPA/U.S. Navy - Office of Naval Research (Contract N00014-80-C-0622)DARPA/U.S. Navy - Office of Naval Research (Contract N00014-87-K-0825)National Science Foundation (Grant ECS-83-10941)AT&T Bell Laboratorie

Global exposure of population and land‐use to meteorological droughts under different warming levels and SSPs: a CORDEX‐based study

Global warming is likely to cause a progressive drought increase in some regions, but how population and natural resources will be affected is still underexplored. This study focuses on global population, forests, croplands and pastures exposure to meteorological drought hazard in the 21st century, expressed as frequency and severity of drought events. As input, we use a large ensemble of climate simulations from the Coordinated Regional Climate Downscaling Experiment (CORDEX), population projections from the NASA-SEDAC dataset and land-use projections from the Land-Use Harmonization 2 project for 1981–2100. The exposure to drought hazard is presented for five Shared Socioeconomic Pathways (SSP1-SSP5) at four Global Warming Levels (GWLs: 1.5°C to 4°C). Results show that considering only Standardized Precipitation Index (SPI; based on precipitation), the SSP3 at GWL4 projects the largest fraction of the global population (14%) to experience an increase in drought frequency and severity (versus 1981–2010), with this value increasing to 60% if temperature is considered (indirectly included in the Standardized Precipitation-Evapotranspiration Index, SPEI). With SPEI, considering the highest GWL for each SSP, 8 (for SSP2, SSP4, SSP5) and 11 (SSP3) billion people, that is, more than 90%, will be affected by at least one unprecedented drought. For SSP5 at GWL4, approximately 2 × 10$^{6}$ km$^{2}$ of forests and croplands (respectively, 6% and 11%) and 1.5 × 10$^{6}$ km$^{2}$ of pastures (19%) will be exposed to increased drought frequency and severity according to SPI, but for SPEI this extent will rise to 17 × 10$^{6}$ km$^{2}$ of forests (49%), 6 × 10$^{6}$ km$^{2}$ of pastures (78%) and 12 × 10$^{6}$ km$^{2}$ of croplands (67%), being mid-latitudes the most affected. The projected likely increase of drought frequency and severity significantly increases population and land-use exposure to drought, even at low GWLs, thus extensive mitigation and adaptation efforts are needed to avoid the most severe impacts of climate change

Custom Integrated Circuits

Contains reports on twelve research projects.Analog Devices, Inc.International Business Machines, Inc.Joint Services Electronics Program (Contract DAAL03-86-K-0002)Joint Services Electronics Program (Contract DAAL03-89-C-0001)U.S. Air Force - Office of Scientific Research (Grant AFOSR 86-0164)Rockwell International CorporationOKI Semiconductor, Inc.U.S. Navy - Office of Naval Research (Contract N00014-81-K-0742)Charles Stark Draper LaboratoryNational Science Foundation (Grant MIP 84-07285)National Science Foundation (Grant MIP 87-14969)Battelle LaboratoriesNational Science Foundation (Grant MIP 88-14612)DuPont CorporationDefense Advanced Research Projects Agency/U.S. Navy - Office of Naval Research (Contract N00014-87-K-0825)American Telephone and TelegraphDigital Equipment CorporationNational Science Foundation (Grant MIP-88-58764

Custom Integrated Circuits

Contains reports on nine research projects.Analog Devices, Inc.International Business Machines CorporationJoint Services Electronics Program Contract DAAL03-89-C-0001U.S. Air Force - Office of Scientific Research Contract AFOSR 86-0164BDuPont CorporationNational Science Foundation Grant MIP 88-14612U.S. Navy - Office of Naval Research Contract N00014-87-K-0825American Telephone and TelegraphDigital Equipment CorporationNational Science Foundation Grant MIP 88-5876

Stratospheric aerosol - Observations, processes, and impact on climate

Interest in stratospheric aerosol and its role in climate have increased over the last decade due to the observed increase in stratospheric aerosol since 2000 and the potential for changes in the sulfur cycle induced by climate change. This review provides an overview about the advances in stratospheric aerosol research since the last comprehensive assessment of stratospheric aerosol was published in 2006. A crucial development since 2006 is the substantial improvement in the agreement between in situ and space-based inferences of stratospheric aerosol properties during volcanically quiescent periods. Furthermore, new measurement systems and techniques, both in situ and space based, have been developed for measuring physical aerosol properties with greater accuracy and for characterizing aerosol composition. However, these changes induce challenges to constructing a long-term stratospheric aerosol climatology. Currently, changes in stratospheric aerosol levels less than 20% cannot be confidently quantified. The volcanic signals tend to mask any nonvolcanically driven change, making them difficult to understand. While the role of carbonyl sulfide as a substantial and relatively constant source of stratospheric sulfur has been confirmed by new observations and model simulations, large uncertainties remain with respect to the contribution from anthropogenic sulfur dioxide emissions. New evidence has been provided that stratospheric aerosol can also contain small amounts of nonsulfate matter such as black carbon and organics. Chemistry-climate models have substantially increased in quantity and sophistication. In many models the implementation of stratospheric aerosol processes is coupled to radiation and/or stratospheric chemistry modules to account for relevant feedback processes

Improved precision on the experimental E0 decay branching ratio of the Hoyle state

Background: Stellar carbon synthesis occurs exclusively via the 3α process, in which three α particles fuse to form 12C in the excited Hoyle state, followed by electromagnetic decay to the ground state. The Hoyle state is above the α threshold, and the rate of stellar carbon production depends on the radiative width of this state. The radiative width cannot be measured directly, and must instead be deduced by combining three separately measured quantities. One of these quantities is the E0 decay branching ratio of the Hoyle state, and the current 10% uncertainty on the radiative width stems mainly from the uncertainty on this ratio. The rate of the 3α process is an important input parameter in astrophysical calculations on stellar evolution, and a high precision is imperative to constrain the possible outcomes of astrophysical models.The project was supported by the Australian Research Council Discovery Grants No. DP140102986, No. DP170101673, and No. DP170102423. Operation of the ANU Heavy Ion Accelerator Facility is supported by the NCRIS HIA capability. The support from technical staff for the development of the pair spectrometer, as well as during the long experimental runs, is greatly appreciated. This work was partially supported by the International Joint Research Promotion Program of Osaka University and JSPS KAKENHI Grant No. JP 17H02893, the Natural Sciences and Engineering Research Council of Canada, the National Research Foundation (NRF), South Africa, under Grants No. 93533 and No. 118645

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types