Summary Background Lithium has neuroprotective effects in cell and animal models of amyotrophic lateral sclerosis (ALS), and a small pilot study in patients with ALS showed a significant effect of ...lithium on survival. We aimed to assess whether lithium improves survival in patients with ALS. Methods The lithium carbonate in amyotrophic lateral sclerosis (LiCALS) trial is a randomised, double-blind, placebo-controlled trial of oral lithium taken daily for 18 months in patients with ALS. Patients aged at least 18 years who had ALS according to the revised El Escorial criteria, had disease duration between 6 and 36 months, and were taking riluzole were recruited from ten centres in the UK. Patients were randomly assigned (1:1) to receive either lithium or matched placebo tablets. Randomisation was via an online system done at the level of the individual by block randomisation with randomly varying block sizes, stratified by study centre and site of disease onset (limb or bulbar). All patients and assessing study personnel were masked to treatment assignment. The primary endpoint was the rate of survival at 18 months and was analysed by intention to treat. This study is registered with Eudract, number 2008-006891-31. Findings Between May 26, 2009, and Nov 10, 2011, 243 patients were screened, 214 of whom were randomly assigned to receive lithium (107 patients) or placebo (107 patients). Two patients discontinued treatment and one died before the target therapeutic lithium concentration could be achieved. 63 (59%) of 107 patients in the placebo group and 54 (50%) of 107 patients in the lithium group were alive at 18 months. The survival functions did not differ significantly between groups (Mantel-Cox log-rank χ2 on 1 df=1·64; p=0·20). After adjusting for study centre and site of onset using logistic regression, the relative odds of survival at 18 months (lithium vs placebo) was 0·71 (95% CI 0·40–1·24). 56 patients in the placebo group and 61 in the lithium group had at least one serious adverse event. Interpretation We found no evidence of benefit of lithium on survival in patients with ALS, but nor were there safety concerns, which had been identified in previous studies with less conventional designs. This finding emphasises the importance of pursuing adequately powered trials with clear endpoints when testing new treatments. Funding The Motor Neurone Disease Association of Great Britain and Northern Ireland.
Parathion is a major pesticide that is used worldwide in large quantities. The kinetics and mechanisms of the sonochemical transformations of p-nitrophenol and hydrogen sulfide in aqueous solutions ...are examined.
L2NAS Mills, Keith G.; Han, Fred X.; Salameh, Mohammad ...
Proceedings of the 30th ACM International Conference on Information & Knowledge Management,
10/2021
Conference Proceeding
Odprti dostop
Neural architecture search (NAS) has achieved remarkable results in deep neural network design. Differentiable architecture search converts the search over discrete architectures into a ...hyperparameter optimization problem which can be solved by gradient descent. However, questions have been raised regarding the effectiveness and generalizability of gradient methods for solving non-convex architecture hyperparameter optimization problems. In this paper, we propose L2NAS, which learns to intelligently optimize and update architecture hyperparameters via an actor neural network based on the distribution of high-performing architectures in the search history. We introduce a quantile-driven training procedure which efficiently trains L2NAS in an actor-critic framework via continuous-action reinforcement learning. Experiments show that L2NAS achieves state-of-the-art results on NAS-Bench-201 benchmark as well as DARTS search space and Once-for-All MobileNetV3 search space. We also show that search policies generated by L2NAS are generalizable and transferable across different training datasets with minimal fine-tuning.
Background
This study aimed to assess the best achievable outcomes in laparoscopic liver resection (LLR) after risk adjustment based on surgical technical difficulty using a national registry.
...Methods
LLRs registered in the Italian Group of Minimally Invasive Liver Surgery registry from November 2014 to March 2018 were considered. Benchmarks were calculated according to the Achievable Benchmark of Care (ABC™). LLRs at each centre were divided into three clusters (groups I, II and III) based on the Kawaguchi classification. ABCs for overall and major morbidity were calculated in each cluster. Multivariable analysis was used to identify independent risk factors for overall and major morbidity. Significant variables were used in further risk adjustment.
Results
A total of 1752 of 2263 patients fulfilled the inclusion criteria: 1096 (62·6 per cent) in group I, 435 (24·8 per cent) in group II and 221 (12·6 per cent) in group III. The ABCs for overall morbidity (7·8, 14·2 and 26·4 per cent for grades I, II and II respectively) and major morbidity (1·4, 2·2 and 5·7 per cent) increased with the difficulty of LLR. Multivariable analysis showed an increased risk of overall morbidity associated with multiple LLRs (odds ratio (OR) 1·35), simultaneous intestinal resection (OR 3·76) and cirrhosis (OR 1·83), and an increased risk of major morbidity with intestinal resection (OR 4·61). ABCs for overall and major morbidity were 14·4 and 3·2 per cent respectively for multiple LLRs, 30 and 11·1 per cent for intestinal resection, and 14·9 and 4·8 per cent for cirrhosis.
Conclusion
Overall morbidity benchmarks for LLR ranged from 7·8 to 26·4 per cent, and those for major morbidity from 1·4 to 5·7 per cent, depending on complexity. Benchmark values should be adjusted according to multiple LLRs or simultaneous intestinal resection and cirrhosis.
Antecedentes
Este estudio tuvo como objetivo evaluar los mejores resultados que se pueden conseguir en la resección hepática laparoscópica (laparoscopic liver resection, LLR) después del ajuste por riesgos basado en la dificultad de la técnica quirúrgica utilizando un registro nacional.
Métodos
Se consideraron las LLRs incluidas en el Registro del Grupo Italiano de Cirugía Hepática Mínimamente Invasiva desde 11/2014 a 03/2018. Los resultados de referencia (benchmarks) se calcularon de acuerdo con el Achievable Benchmark of Care (ABC™). Las LLRs de cada uno de los centros se dividieron en 3 grupos (Grupo I, II y III) en base a la clasificación de Kawaguchi. Se calculó el ABC de la morbilidad global y de la morbilidad mayor para cada grupo. Se realizó un análisis multivariable para identificar los factores independientes de riesgos para la morbilidad global y morbilidad mayor. Se utilizaron variables significativas para realizar ajustes de riesgo adicionales.
Resultados
Un total de 1.752 pacientes de los 2.263 cumplían los criterios de inclusión, de los cuales 1.096 (62,6%) se incluyeron en el Grupo I, 435 (24,8%) en el Grupo II y 221 (12,6%) en el Grupo III. El ABC de la morbilidad global (7,8%, 14,2%, 26,4%) y de la morbilidad mayor (1,4%, 2,2%, 5,7%) aumentó del Grupo I al Grupo III. El análisis multivariable mostró un incremento del riesgo para la morbilidad global asociada con múltiples LLRs (razón de oportunidades, odds ratio, OR 1,349), resección intestinal simultánea (OR 3,760) y cirrosis (OR 1,825), y para la morbilidad mayor con la resección intestinal (OR 4,606). Los ABC de la morbilidad global y morbilidad mayor fueron 14,4% y 3,2% para las LLR múltiples, 30% y 11% para la resección intestinal, y 14,9% y 4,8% para la cirrosis, respectivamente.
Conclusión
Los resultados de referencia (benchmark) para la morbilidad global y morbilidad mayor en la LLR variaron entre un 8% y un 26% y entre un 1,4% y un 5,7%, dependiendo de la complejidad. Los valores de referencia deberían ajustarse de acuerdo con la práctica de LLRs múltiples o resección intestinal simultánea y cirrosis.
Data from the I Go MILS registry were used to calculate the benchmarks for outcomes in laparoscopic liver resection (LLR). Depending on the technical complexity of LLR, the benchmarks ranged between 7·8 and 26·4 per cent for overall morbidity, and 1·4 and 5·7 per cent for major morbidity. Multiple LLRs, simultaneous intestinal resection and cirrhosis worsened benchmark values.
Benchmarks may be useful
Background
Surgical outcomes may be associated with hospital volume and the influence of volume on minimally invasive liver surgery (MILS) is not known.
Methods
Patients entered into the prospective ...registry of the Italian Group of MILS from 2014 to 2018 were considered. Only centres with an accrual period of at least 12 months and stable MILS activity during the enrolment period were included. Case volume was defined by the mean number of minimally invasive liver resections performed per month (MILS/month).
Results
A total of 2225 MILS operations were undertaken by 46 centres; nine centres performed more than two MILS/month (1376 patients) and 37 centres carried out two or fewer MILS/month (849 patients). The proportion of resections of anterolateral segments decreased with case volume, whereas that of major hepatectomies increased. Left lateral sectionectomies and resections of anterolateral segments had similar outcome in the two groups. Resections of posterosuperior segments and major hepatectomies had higher overall and severe morbidity rates in centres performing two or fewer MILS/month than in those undertaking a larger number (posterosuperior segments resections: overall morbidity 30·4 versus 18·7 per cent respectively, and severe morbidity 9·9 versus 4·0 per cent; left hepatectomy: 46 versus 22 per cent, and 19 versus 5 per cent; right hepatectomy: 42 versus 34 per cent, and 25 versus 15 per cent).
Conclusion
A volume–outcome association existed for minimally invasive hepatectomy. Complex and major resections may be best managed in high‐volume centres.
Antecedentes
Los resultados quirúrgicos pueden estar relacionados con el volumen de casos del hospital, pero no se conoce la influencia en la cirugía mínimamente invasiva del hígado (minimally‐invasive liver surgery, MILS).
Métodos
Se incluyeron los pacientes registrados en el registro prospectivo del grupo italiano de MILS desde 2014 a 2018. Solo se consideraron centros con extensión de ≥ 12 meses y actividad estable de MILS durante el periodo de reclutamiento. El volumen de casos se definió como el número de MILS efectuado por mes.
Resultados
Se llevaron a cabo un total de 2.225 MILS en 46 centros, 9 de ellos con > 2 MILS/mes (n = 1.376 pacientes) y 37 centros con ≤ 2 MILS/mes (n = 849). La proporción de resecciones de segmentos anterolaterales disminuyó con el volumen de casos, mientras que la proporción de hepatectomías mayores aumentó. Los resultados para ambos grupos fueron similares en las seccionectomías lateral izquierda y en las resecciones del segmento anterolateral. Las resecciones del segmento posterosuperior y las hepatectomías mayores presentaron tasas más altas de morbilidad global y morbilidad grave en centros que realizaban ≤ 2 MILS/mes que en los que realizaban > 2 MILS/mes (resecciones del segmento posterosuperior, morbilidad global 30,4 versus 18,7%, morbilidad grave 9,9 versus 4,0%; hepatectomía izquierda, 46,2 versus 22,0%, 19,2 versus 5,5%; hepatectomía derecha, 41,7 versus 33,8%, 25,0 versus 14.9%).
Conclusión
Se observó una asociación volumen‐resultado para la resección hepática mínimamente invasiva. Las resecciones complejas y mayores se pueden manejar mejor en centros de gran volumen.
The present study investigated the impact of the hospital case volume on minimally invasive liver surgery (MILS). It was based on the prospective registry of the Italian Group of Minimally Invasive Liver Surgery and analysed 2225 patients undergoing MILS in 46 centres. The centre case volume for MILS did not influence the outcome of standard minor hepatectomies; however, it did influence the outcome of complex hepatectomies (resection of posterosuperior segments and major hepatectomies), for which low‐volume centres had higher morbidity rates than high‐volume centres.
Size matters
The aim of this study was to compare the perioperative outcomes of robotic liver surgery (RLS) and laparoscopic liver surgery (LLS) in various settings.
Clear advantages of RLS over LLS have rarely ...been demonstrated, and the associated costs of robotic surgery are generally higher than those of laparoscopic surgery. Therefore, the exact role of the robotic approach in minimally invasive liver surgery remains to be defined.
In this international retrospective cohort study, the outcomes of patients who underwent RLS and LLS for all indications between 2009 and 2021 in 34 hepatobiliary referral centers were compared. Subgroup analyses were performed to compare both approaches across several types of procedures: minor resections in the anterolateral (2, 3, 4b, 5, and 6) or posterosuperior segments (1, 4a, 7, 8), and major resections (≥3 contiguous segments). Propensity score matching (PSM) was used to mitigate the influence of selection bias. The primary outcome was textbook outcome in liver surgery (TOLS), previously defined as the absence of intraoperative incidents ≥grade 2, postoperative bile leak ≥grade B, severe morbidity, readmission, and 90-day or in-hospital mortality with the presence of an R0 resection margin in case of malignancy. The absence of a prolonged length of stay was added to define TOLS+.
Among the 10.075 included patients, 1.507 underwent RLS and 8.568 LLS. After PSM, both groups constituted 1.505 patients. RLS was associated with higher rates of TOLS (78.3% vs. 71.8%, P<0.001) and TOLS+ (55% vs. 50.4%, P=0.026), less Pringle usage (39.1% vs. 47.1%, P<0.001), blood loss (100 vs. 200 milliliters, P<0.001), transfusions (4.9% vs. 7.9%, P=0.003), conversions (2.7% vs 8.8%, P<0.001), overall morbidity (19.3% vs. 25.7%, P<0.001) and R0 resection margins (89.8% vs. 86%, P=0.015), but longer operative times (190 vs. 210 min, P=0.015). In the subgroups, RLS tended to have higher TOLS rates, compared to LLS, for minor resections in the posterosuperior segments (n=431 per group, 75.9% vs. 71.2%, P=0.184) and major resections (n=321 per group, 72.9% vs. 67.5%, P=0.086), although these differences did not reach statistical significance.
While both producing excellent outcomes, RLS might facilitate slightly higher TOLS rates than LLS.
This book was first published in 2004. Plato, Aristophanes and the creators of the 'Orphic' gold tablets employ the traditional tale of a journey to the realm of the dead to redefine, within the ...mythic narrative, the boundaries of their societies. Rather than being the relics of a faded ritual tradition or the products of Orphic influence, these myths can only reveal their meanings through a close analysis of the specific ways in which each author makes use of the tradition. For these authors, myth is an agonistic discourse, neither a kind of sacred dogma nor a mere literary diversion, but rather a flexible tool that serves the wide variety of uses to which it is put. The traditional tale of the journey to the Underworld in Greek mythology is neither simple nor single, but each telling reveals a perspective on the cosmos, a reflection of the order of this world through the image of the other.
With the European Parliament comprising politicians from many different countries, cultures, languages, national parties and institutional backgrounds, one might expect politics in the Parliament to ...be highly-fragmented and unpredictable. By studying more than 12,000 recorded votes between 1979 and 2004 this 2007 book establishes that the opposite is in fact true: transnational parties in the European Parliament are highly cohesive and the classic 'left-right' dimension dominates voting behaviour. Furthermore, the cohesion of parties in the European Parliament has increased as the powers of the Parliament have increased. The authors suggest that the main reason for these developments is that like-minded MEPs have incentives to form stable transnational party organizations and to use these organizations to compete over European Union policies. They suggest that this is a positive development for the future of democratic accountability in the European Union.
Seabed fluid flow involves the flow of gases and liquids through the seabed. Such fluids have been found to leak through the seabed into the marine environment in seas and oceans around the world - ...from the coasts to deep ocean trenches. This geological phenomenon has widespread implications for the sub-seabed, seabed, and marine environments. Seabed fluid flow affects seabed morphology, mineralization, and benthic ecology. Natural fluid emissions also have a significant impact on the composition of the oceans and atmosphere; and gas hydrates and hydrothermal minerals are potential future resources. This book describes seabed fluid flow features and processes, and demonstrates their importance to human activities and natural environments. It is targeted at research scientists and professionals with interests in the marine environment. Colour versions of many of the illustrations, and additional material - most notably feature location maps - can be found at www.cambridge.org/9780521819503.
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